CN115487319A - Preparation method and application of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages - Google Patents
Preparation method and application of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages Download PDFInfo
- Publication number
- CN115487319A CN115487319A CN202211131148.XA CN202211131148A CN115487319A CN 115487319 A CN115487319 A CN 115487319A CN 202211131148 A CN202211131148 A CN 202211131148A CN 115487319 A CN115487319 A CN 115487319A
- Authority
- CN
- China
- Prior art keywords
- photomagnetic
- bimodal
- tumor
- associated macrophages
- oleic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 88
- 210000004981 tumor-associated macrophage Anatomy 0.000 title claims abstract description 46
- 230000002902 bimodal effect Effects 0.000 title claims abstract description 45
- 230000008685 targeting Effects 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims abstract description 36
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims abstract description 36
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims abstract description 36
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000005642 Oleic acid Substances 0.000 claims abstract description 36
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims abstract description 36
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims abstract description 36
- 229920000642 polymer Polymers 0.000 claims abstract description 26
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000243 solution Substances 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- 238000003756 stirring Methods 0.000 claims description 20
- 238000001035 drying Methods 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 16
- 235000003891 ferrous sulphate Nutrition 0.000 claims description 15
- 239000011790 ferrous sulphate Substances 0.000 claims description 15
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 15
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 15
- 229910000359 iron(II) sulfate Inorganic materials 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 15
- 239000012153 distilled water Substances 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 10
- 238000000502 dialysis Methods 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 239000012528 membrane Substances 0.000 claims description 10
- 239000011259 mixed solution Substances 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- 238000003384 imaging method Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 239000002244 precipitate Substances 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 238000005481 NMR spectroscopy Methods 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 5
- 239000007795 chemical reaction product Substances 0.000 claims description 5
- 238000011161 development Methods 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 238000011049 filling Methods 0.000 claims description 5
- 238000000799 fluorescence microscopy Methods 0.000 claims description 5
- 239000003517 fume Substances 0.000 claims description 5
- 230000007935 neutral effect Effects 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 4
- 239000008346 aqueous phase Substances 0.000 claims description 4
- 230000001413 cellular effect Effects 0.000 claims description 4
- 230000009401 metastasis Effects 0.000 claims description 4
- 238000012544 monitoring process Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 239000004698 Polyethylene Substances 0.000 claims description 3
- 229920000573 polyethylene Polymers 0.000 claims description 3
- 239000008363 phosphate buffer Substances 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims description 2
- 239000012266 salt solution Substances 0.000 claims description 2
- 230000008021 deposition Effects 0.000 claims 1
- 239000011248 coating agent Substances 0.000 abstract description 6
- 238000000576 coating method Methods 0.000 abstract description 6
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 abstract description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 19
- 206010028980 Neoplasm Diseases 0.000 description 19
- 210000002540 macrophage Anatomy 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 238000009169 immunotherapy Methods 0.000 description 7
- 239000002086 nanomaterial Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 238000002189 fluorescence spectrum Methods 0.000 description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
- 239000008055 phosphate buffer solution Substances 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000002872 contrast media Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 238000011503 in vivo imaging Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 238000000584 ultraviolet--visible--near infrared spectrum Methods 0.000 description 2
- 102100021723 Arginase-1 Human genes 0.000 description 1
- 101710129000 Arginase-1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 108090000176 Interleukin-13 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 210000005006 adaptive immune system Anatomy 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000012984 biological imaging Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000002961 echo contrast media Substances 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 210000001357 hemopoietic progenitor cell Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000001167 microscope projection photolithography Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
- 229940031182 nanoparticles iron oxide Drugs 0.000 description 1
- 239000002405 nuclear magnetic resonance imaging agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 238000005424 photoluminescence Methods 0.000 description 1
- 208000017983 photosensitivity disease Diseases 0.000 description 1
- 231100000434 photosensitization Toxicity 0.000 description 1
- 238000007626 photothermal therapy Methods 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 239000002096 quantum dot Substances 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0065—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle
- A61K49/0067—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle quantum dots, fluorescent nanocrystals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/12—Macromolecular compounds
- A61K49/126—Linear polymers, e.g. dextran, inulin, PEG
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1833—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
- A61K49/1827—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1851—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
- A61K49/1857—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
- A61K49/186—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA the organic macromolecular compound being polyethyleneglycol [PEG]
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Medical Informatics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Pharmacology & Pharmacy (AREA)
- Crystallography & Structural Chemistry (AREA)
- Immunology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a preparation method and application of a photomagnetic bimodal nanoparticle targeting tumor-associated macrophages, which comprises the following steps: 1) preparing a carbonized polymer dot, 2) coating ferroferric oxide with oleic acid, and 3) coating the carbonized polymer dot and the ferroferric oxide with distearoyl phosphatidyl ethanolamine-polyethylene glycol-D mannose.
Description
Technical Field
The invention relates to the field of nanoparticle medicines, in particular to a preparation method and application of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages.
Background
Tumor immunotherapy has become a breakthrough in cancer therapy by activating the innate and adaptive immune system to eliminate tumors. Although some results have been achieved in the tests, some problems remain to be solved, such as limited persistent response rate, immune-related side effects, etc., and the current clinical application of tumor immunotherapy in solid tumors is limited.
The Tumor Microenvironment (TME) is a significant cause of tumor immune escape and treatment failure. Tumor-associated macrophages (TAMs) are an important component of TME, often associated with poor prognosis and drug resistance, which have become promising targets in cancer immunotherapy.
The nano technology is a scientific research field of multiple disciplines, and with the development of the nano biotechnology, the nano material has attracted wide attention in tumor immunotherapy due to the advantages of the nano material in the aspects of targeted drug delivery, accurate positioning drug release, simple surface functionalization, biological activity and the like. Nano immunotherapy is a treatment method based on nano materials, and the treatment effect of immunotherapy is improved by regulating immunosuppressive microenvironment, so that the immune system is activated through interaction with other immune cells.
TAMs are functionally heterogeneous, divided into two major subgroups, M1-type and M2-type macrophages. Induced into M1 type by Lipopolysaccharide (LPS), M1 type macrophages secrete antibacterial molecules and proinflammatory cytokines including Reactive Oxygen Species (ROS), nitric Oxide (NO) and IL-6 through the classical activation pathway. M1-type macrophages also retain potent antigen presenting ability, inducing a strong Th1 response. In contrast, M2-type macrophages are activated by IL-4, IL-13, IL-10, CSF-1, and the like, and preferentially secrete anti-inflammatory cytokines, including transforming growth factor beta (TGF-. Beta.), IL-10, and proteases such as arginase-1 and MPPs. M2-type macrophages play a key role in limiting immune responses, inducing angiogenesis, and tissue repair. Thus, type M2 TAMs are associated with tumorigenic activity, whereas type M1 TAMs are associated with antitumor activity.
Nanotechnology has great prospect in improving the tumor immunotherapy effect. Given the role of TAMs in inhibiting anti-tumor immunity, various nanotechnological approaches have been developed to target TAMs, including termination of macrophage recruitment, interference with TAM survival, and reprogramming M2-type TAMs to M1-type. The targeting of TAMs by nanomaterials specifically enhances anti-tumor immune responses, and the above technical approaches have shown great potential.
Carbon nanodots (CDs) are carbonaceous nanomaterials of less than 10nm found in the beginning of the 21 st century, usually consisting of Carbon, hydrogen and oxygen. CDs are promising nano materials which can be applied to different fields, are green and environment-friendly nano materials because the CDs do not contain toxic metal elements, and can expand wider space in the field of biological science. Secondly, the carbon dots are used for biomarkers and biological imaging due to strong photobleaching resistance, no flicker and low biological toxicity; the fluorescent probe is used for biosensing due to the fluorescent quenching effect; the infrared absorption, the photothermal effect and the photosensitization are realized, so that the preparation method is applied to photothermal therapy and photodynamic therapy technologies; the material has good physical and chemical properties and is used for luminescent materials, such as laser, LED and the like. The study utilized the long wavelength near infrared fluorescence properties of carbon nanodots for imaging. Carbon dots have relevance in many biomedical fields due to their photoluminescence properties, low toxicity and their emission properties in comparison to other quantum dots, and their emission properties can be tuned within a bio-transparent window (600-1100 nm), which provides a special contrast for in vivo applications of fluorescence imaging in tumor diagnosis and in vivo imaging, etc. The penetration of different light sources in biological tissue is different, only long-wave emission (from red to near infrared) can reach deep tissues, and the damage caused by the long-wave emission is negligible. Therefore, it is desirable to tune the emission of CDs to the near infrared region, which is also necessary for cancer therapy applications. The carbon dots of this study have this near infrared emission characteristic.
Superparamagnetic iron oxide nanoparticles (SPIONs) are FDA-approved materials, consist of Fe3O4 (II, III) oxide nanocrystals, and have wide applications in targeted drug therapy, magnetic hyperthermia, focused ultrasound, and magnetic resonance imaging contrast agents. SPIONs, which are typically less than 30nm in diameter, can alter the relaxation rate of tissue, and can be used for contrast enhancement in T1 and T2 weighted Magnetic Resonance Imaging (MRI), detection and imaging of tissue. The nano particle consisting of Fe3O4 has obvious T2 signal reduction characteristic and can be used for nuclear magnetic negative imaging, T2 can be quantitatively analyzed, and further proves that iron in the nano particle has the characteristics of a nuclear magnetic negative contrast agent, and the iron is very common, safe and conventional for clinical nuclear magnetic resonance negative contrast agents. In recent years, fe3O4 nanoparticles are receiving more and more attention, and the literature reports that the Fe3O4 nanoparticles can not only kill tumor cells by generating ROS through Fenton reaction with H2O2 over-expressed in the tumor cells, but also kill the tumor cells
Can polarize TAMs into M1 type, and has antitumor effect. TAMs are considered as potential effective targets for cancer treatment, ranging from M2, which promotes tumor growth, to M1, which inhibits tumor growth.
The selection of the current tumor clinical treatment method is usually based on single pathological biopsy and cannot reflect the overall condition of the disease of a patient. The tumor microenvironment plays a key role in tumor development, such as tumor drug resistance, local escape, distant metastasis and the like. Immunotherapy of tumors is a new direction for tumor therapy, but has limited effect on solid tumors such as colorectal cancer.
Disclosure of Invention
The invention provides a preparation method and application of a photomagnetic bimodal nanoparticle targeting tumor-associated macrophages, and aims to solve the problems in the prior art.
A preparation method of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages comprises the following steps:
1) Preparing a carbonized polymer dot, weighing 50mg of p-toluenesulfonate, placing in a small bottle, adding polyethylene glycol by using a pipettor, uniformly mixing, transferring the completely mixed solution into a reaction kettle by using the pipettor, placing in an oven, and keeping at 180 ℃ for 8 hours; filtering the reaction product with a 0.22um filter membrane; filling the filtered solution into a 3500 dialysis membrane for dialysis, and changing water every 6 hours for 4-6 times; centrifuging the seeped substances, removing supernatant, putting the obtained solid substances into a drying oven at 60 ℃ for drying for about 2 hours, and collecting solid carbon points to obtain carbonized polymer points;
2) Oleic acid-coated ferroferric oxide, ferrous sulfate and ferric chloride are added into distilled water under the stirring state, and the weight ratio of ferrous sulfate: ferric chloride: distilled water =1: 1:8-12, adding 1ml ammonia water to generate black precipitate, and adding 2ml oleic acid; then, heating to 80 ℃ under the protection of nitrogen at the stirring speed of 300r/min, and reacting for 2 hours; finally, washing the product to be neutral, and drying the product in an oven at the temperature of 60-80 ℃ for 4-6h to obtain Fe coated with oleic acid 3 O 4 Nanoparticles;
3) Adding distearoylphosphatidylethanolamine-polyethylene glycol-D-mannose-coated carbonized polymer dots and ferroferric oxide, taking 5mg of the carbonized polymer dots, taking 40mg of DSPE-PEG-mannose, placing in a 5ml small bottle, adding an organic solution in a fume hood, taking 1ml of oleic acid-coated Fe 3 O 4 Adding the nano particles into a small bottle, uniformly mixing under ultrasonic, adding 50ml of water into a round-bottom flask, adding the uniformly mixed solution onto the liquid level of the round-bottom flask, making the solution out of the sun, placing the solution into a heating stirrer, keeping the temperature at 40-80 ℃, and stirring at the rotation speed of 550-650 revolutions per minute until the organic solution is completely volatilized;
spin-drying the residual solution in the round-bottom flask by using a rotary evaporator to obtain a solid substance; adding 10ml phosphate buffer salt solution for dissolving, collecting by using a 20ml syringe, filtering by using an aqueous phase 0.44um filter, placing in a small bottle for later use, and performing dark preservation by using tinfoil to obtain the photomagnetic bimodal nanoparticles targeting tumor-associated macrophages.
As a preferable technical scheme, in the step 2), 500mg of ferrous sulfate and 500mg of ferric trichloride are added into 5ml of distilled water to be fully reacted, 1ml of ammonia water is added to generate black precipitate, and 2ml of oleic acid is added after the temperature is kept constant; according to the weight ratio of ferrous sulfate: ferric chloride: distilled water =1: 1.
As a preferred technical solution, the oleic acid-coated Fe in the step 3) is 3 O 4 The nano particle is 5mg/ml Fe coated with oleic acid 3 O 4 Nanoparticles.
As a preferable technical scheme, the carbonized polymer dots in the step 3) are Fe coated with oleic acid 3 O 4 The mass ratio of the nanoparticles to the DSPE-PEG-mannose is 1:1:8.
as a preferable technical scheme, the organic solvent in the step 3) is one of tetrahydrofuran and toluene.
As a preferable technical scheme, the step 3) is arranged in a heating stirrer, the temperature is 60 ℃, and the stirring speed is 600 revolutions until the organic solution is completely volatilized.
As a preferable technical scheme, the nano particles in the step 3) are magneto-optical bimodal nano particles DSPE-PEG-Man @ Fe3O4-Cds.
The invention also discloses an application of the photomagnetic bimodal nanoparticle DSPE-PEG-Man @ Fe3O4-CdS targeting tumor-related macrophages in colorectal cancer and metastasis.
The photomagnetic bimodal nanoparticles targeting the tumor-associated macrophages perform non-invasive monitoring on the occurrence, development and outcome of diseases at the cellular and molecular level through nuclear magnetic resonance negative imaging and infrared fluorescence imaging.
The invention discloses a preparation method and application of a photomagnetic bimodal nanoparticle targeting tumor-associated macrophages, which comprises the following steps: 1) Preparing a carbonized polymer dot, weighing 50mg of p-toluenesulfonate, placing in a small bottle, adding polyethylene glycol by using a pipettor, uniformly mixing, transferring the completely mixed solution into a reaction kettle by using the pipettor, placing in an oven, and keeping at 180 ℃ for 8 hours; filtering the reaction product with a 0.22um filter membrane; filling the filtered solution into a 3500 dialysis membrane for dialysis, and changing water every 6 hours for 4-6 times; is permeated byCentrifuging the precipitated substances, removing supernatant, drying the obtained solid substances in an oven at 60 ℃ for about 2 hours, and collecting solid carbon points to obtain carbonized polymer points; 2) The preparation method comprises the following steps of coating ferroferric oxide with oleic acid, adding ferrous sulfate and ferric trichloride into a proper amount of distilled water under a stirring state to enable the ferrous sulfate and the ferric trichloride to fully react, adding ammonia water to generate black precipitate, and adding the oleic acid after the temperature is constant; then, heating to 80 ℃ under the protection of nitrogen at the stirring speed of 300r/min, and reacting for 2 hours; finally, washing the product to be neutral, and drying the product in an oven at 60-80 ℃ for 4-6h to obtain Fe coated with oleic acid 3 O 4 Nanoparticles; 3) Adding distearoylphosphatidylethanolamine-polyethylene glycol-D-mannose-coated carbonized polymer dots and ferroferric oxide, taking 5mg of the carbonized polymer dots, taking 40mg of DSPE-PEG-mannose, placing in a 5ml small bottle, adding an organic solution in a fume hood, taking 1ml of oleic acid-coated Fe 3 O 4 Adding the nano particles into a small bottle, uniformly mixing under ultrasonic, adding 50ml of water into a round-bottom flask, adding the uniformly mixed solution onto the liquid level of the round-bottom flask, making the solution out of the sun, placing the solution into a heating stirrer, keeping the temperature at 40-80 ℃, and stirring at the rotation speed of 550-650 revolutions per minute until the organic solution is completely volatilized; spin-drying the residual solution in the round-bottom flask by using a rotary evaporator to obtain a solid substance; adding 10ml phosphate buffer solution for dissolving, collecting with 20ml syringe, filtering with 0.44um water phase filter, placing in small bottle for use, and storing with tinfoil in dark place to obtain nanoparticles.
The advantages are that:
1. the nano-particle of the invention combines Magnetic Resonance Imaging (MRI) negative imaging and infrared fluorescence imaging for the first time, and utilizes two methods to carry out in vivo imaging, thereby carrying out non-invasive monitoring and research on the occurrence, development and transfer of diseases from the cellular and molecular level.
2. The nano-particles not only have the function of photomagnetic bimodal imaging, but also can effectively target tumor-associated macrophages (TAMs), carry out the polarization conversion on the TAMs, activate the tumor microenvironment in an immunosuppression state, and treat colorectal cancer diseases from the direction of autoimmunity.
Drawings
FIG. 1 is an ultraviolet-visible-near infrared spectrum of photomagnetic bimodal nanoparticles DSPE-PEG-Man @ Fe3O4-CdS targeted at tumor-associated macrophages in an experiment of the present invention;
FIG. 2 is a visible fluorescence spectrum of a photomagnetic bimodal nanoparticle DSPE-PEG-Man @ Fe3O4-CdS targeting tumor-associated macrophages in an experiment of the present invention;
FIG. 3 is an electron microscope image of photomagnetic bimodal nanoparticles DSPE-PEG-Man @ Fe3O4-CdS targeting tumor-associated macrophages in an experiment of the present invention;
FIG. 4 is a graph of the particle size of the photomagnetic bimodal nanoparticle DSPE-PEG-Man @ Fe3O4-CdS targeting tumor-associated macrophages in an experiment of the present invention;
FIG. 5 is a diagram of the photomagnetic bimodal nanoparticle DSPE-PEG-Man @ Fe3O4-CdS potential of tumor-associated macrophages targeted in an experiment of the present invention;
FIG. 6 is an imaging diagram of nuclear magnetic resonance T1WI of photomagnetic bimodal nanoparticles DSPE-PEG-Man @ Fe3O4-Cds targeting tumor-associated macrophages in the experiment of the present invention.
Detailed Description
In order to make up for the above deficiencies, the invention provides a preparation method and application of a photomagnetic bimodal nanoparticle targeting tumor-associated macrophages, so as to solve the problems in the background art.
A preparation method of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages comprises the following steps:
1) Preparing a carbonized polymer dot, weighing 50mg of p-toluenesulfonate, placing in a small bottle, adding polyethylene glycol by using a pipettor, uniformly mixing, transferring the completely mixed solution into a reaction kettle by using the pipettor, placing in an oven, and keeping at 180 ℃ for 8 hours; filtering the reaction product with a 0.22um filter membrane; filling the filtered solution into a 3500 dialysis membrane for dialysis, and changing water every 6 hours for 4-6 times; centrifuging the seeped substances, removing supernatant, putting the obtained solid substances into a drying oven at 60 ℃ for drying for about 2 hours, and collecting solid carbon points to obtain carbonized polymer points;
2) Oleic acid-coated ferroferric oxide, ferrous sulfate and ferric chloride are added into distilled water under the stirring state, and the weight ratio of ferrous sulfate: ferric chloride: distilled water =1: 1:8-12, adding 1ml ammonia water to generate black precipitate, and adding 2ml oleic acid; then, heating to 80 ℃ under the protection of nitrogen at the stirring speed of 300r/min, and reacting for 2 hours; finally, washing the product to be neutral, and drying the product in an oven at the temperature of 60-80 ℃ for 4-6h to obtain Fe3O4 nano particles coated with oleic acid;
3) Distearoyl phosphatidyl ethanolamine-polyethylene glycol-D mannose coating carbonized polymer dots and ferroferric oxide, taking 5mg of the carbonized polymer dots, taking 40mg of DSPE-PEG-mannose, placing the DSPE-PEG-mannose in a 5ml small bottle, adding an organic solution in a fume hood, taking 1ml of oleic acid coating Fe3O4 nano particles, adding the nano particles into the small bottle, uniformly mixing under ultrasound, then adding 50ml of water into the round bottom flask, adding the uniformly mixed solution onto the liquid surface of the round bottom flask, shielding light, placing the round bottom flask in a heating stirrer, keeping the temperature at 40-80 ℃, and stirring at the rotation speed of 550-650 revolutions per minute until the organic solution is completely volatilized;
spin-drying the residual solution in the round-bottom flask by using a rotary evaporator to obtain a solid substance; adding 10ml phosphate buffer solution for dissolving, collecting with a 20ml syringe, filtering with an aqueous phase 0.44um filter, placing in a small bottle for later use, and storing in dark with tinfoil to obtain the photomagnetic bimodal nanoparticles targeting tumor-associated macrophages.
Adding 500mg of ferrous sulfate and 500mg of ferric trichloride into 5ml of distilled water in the step 2), fully reacting, adding 1ml of ammonia water to generate a black precipitate, and adding 2ml of oleic acid after keeping the temperature constant; according to the weight ratio of ferrous sulfate: ferric chloride: distilled water =1: 1.
The Fe coated with oleic acid in the step 3) 3 O 4 The nano particle is 5mg/ml Fe coated with oleic acid 3 O 4 Nanoparticles.
The carbonized polymer dots in the step 3) are Fe coated with oleic acid 3 O 4 The mass ratio of the nanoparticles to the DSPE-PEG-mannose is 1:1:8.
the organic solvent in the step 3) is one of tetrahydrofuran and toluene.
And (3) placing the organic solution in a heating stirrer at the temperature of 60 ℃ and the stirring speed of 600 revolutions until the organic solution is completely volatilized.
The nano particles in the step 3) are photomagnetic bimodal nano particles DSPE-PEG-Man @ Fe3O4-CdS.
The invention also discloses an application of the photomagnetic bimodal nanoparticle DSPE-PEG-Man @ Fe3O4-CdS targeting tumor-related macrophages in colorectal cancer and metastasis.
The photomagnetic bimodal nanoparticles targeting tumor-associated macrophages perform non-invasive monitoring on the occurrence, development and regression of diseases at the cellular and molecular level through nuclear magnetic resonance negative imaging and infrared fluorescence imaging.
In order to make the technical means, the creation characteristics, the achievement purposes and the effects of the invention easy to understand, the invention is further described with the specific embodiments.
Example 1:
1) Preparing a carbonized polymer dot, weighing 50mg of p-toluenesulfonate, placing in a small bottle, adding polyethylene glycol by using a liquid transfer machine, uniformly mixing, transferring the completely mixed solution into a reaction kettle by using the liquid transfer machine, placing in an oven, and placing at 180 ℃ for 8 hours; filtering the reaction product with a 0.22um filter membrane; filling the filtered solution into a 3500 dialysis membrane for dialysis, and changing water every 6 hours for 4-6 times; centrifuging the precipitated substances, removing supernatant, drying the obtained solid substances in an oven at 60 ℃ for about 2 hours, and collecting solid carbon points to obtain carbonized polymer points;
2) Oleic acid-coated ferroferric oxide, 500mg of ferrous sulfate and 500mg of ferric chloride are added into 5ml of distilled water under the stirring state to fully react, 1ml of ammonia water is added to generate black precipitate, and 2ml of oleic acid is added after the constant temperature; then, heating to 80 ℃ under the protection of nitrogen at the stirring speed of 300r/min, and reacting for 2 hours; finally, washing the product to be neutral, and drying the product in an oven at the temperature of 60-80 ℃ for 4-6h to obtain Fe coated with oleic acid 3 O 4 Nanoparticles;
3) Distearoyl phosphatidyl ethanolamine-polyethylene glycol-D mannose coating carbonized polymer dots and ferroferric oxideTaking 5mg of the carbonized polymer dots, taking 40mg of DSPE-PEG-mannose, placing in a 5ml small bottle, adding organic solution in a fume hood, taking 1ml of Fe coated with oleic acid 3 O 4 Adding the nano particles into a small bottle, uniformly mixing under ultrasonic, adding 50ml of water into a round-bottom flask, adding the uniformly mixed solution onto the liquid level of the round-bottom flask, making the solution out of the sun, placing the solution into a heating stirrer, keeping the temperature at 40-80 ℃, and stirring at the rotation speed of 550-650 revolutions per minute until the organic solution is completely volatilized;
spin-drying the residual solution in the round-bottom flask by using a rotary evaporator to obtain a solid substance; adding 10ml phosphate buffer solution for dissolving, collecting with a 20ml syringe, filtering with an aqueous phase 0.44um filter, placing in a small bottle for later use, and storing in dark with tinfoil to obtain the photomagnetic bimodal nanoparticles targeting tumor-associated macrophages.
The Fe coated with oleic acid in the step 3) 3 O 4 The nano particle is 5mg/ml Fe coated with oleic acid 3 O 4 Nanoparticles.
The carbonized polymer dots in the step 3) are Fe coated with oleic acid 3 O 4 The mass ratio of the nanoparticles to the DSPE-PEG-mannose is 1:1:8.
the organic solvent in the step 3) is one of tetrahydrofuran and toluene.
And (3) placing the organic solution in a heating stirrer at the temperature of 60 ℃ and the stirring speed of 600 revolutions until the organic solution is completely volatilized.
The nano particles in the step 3) are photomagnetic bimodal nano particles DSPE-PEG-Man @ Fe3O4-Cds.
Experiment 1:
the photomagnetic bimodal nanoparticles targeting tumor-associated macrophages prepared in this example 1 were characterized
1. The absorption spectrum of a photomagnetic bimodal nanoparticle (DSPE-PEG-Man @ Fe3O4-CdS) targeting tumor-associated macrophages is measured by using a Shimadzu 3600 ultraviolet-visible-near infrared spectrophotometer.
2. The fluorescence spectrum of the DSPE-PEG-Man @ Fe3O4-CdS nanoparticles was measured by Shimadzu RF-5301PC fluorescence spectrometer.
3. The morphology was observed by a Transmission Electron Microscope (TEM) of JEM-2100F, manufactured by Japan Electron.
4. The X-ray electron energy spectrum of the nanoparticles was measured by a high-resolution ultraviolet electron spectrometer.
5. Absolute fluorescence quantum yield and near infrared emission spectra were determined by an Edinburgh Instrument FLS920 steady state transient fluorescence spectrometer.
6. The fluorescence characteristics of the material were photographed using a fluorescence camera.
7. The material was imaged with T2WI and T2Map using a siemens 3.0T magnetic resonance scanner.
The results are shown below:
1. the ultraviolet-visible-near infrared spectrum (shown in figure 1) of the DSPE-PEG-Man @ Fe3O4-Cpds nano-particle shows that the nano-particle has better near infrared luminescence property.
2. Visible fluorescence spectra of DSPE-PEG-Man @ Fe3O4-Cpds nanoparticles (see FIG. 2).
3. Transmission electron microscopy shows that the DSPE-PEG-Man @ Fe3O4-Cpds nanoparticles have the characteristics of good dispersibility, uniform particle size and morphology and spherical structure (see figure 3).
DSL showed that the average size of the DSPE-PEG-Man @ Fe3O4-Cpds particle size was 141nm, and the particle size distribution was normal (see FIG. 4).
DSL measurements DSPE-PEG-Man @ Fe3O4-Cpds nanoparticle potential are shown, with a kurtosis potential of-17 mV (see FIG. 5).
4. Nuclear resonance showed T2WI images of nanoparticles at concentrations of 0ug/ml, 10ug/ml, 50ug/ml, 100ug/ml, 200ug/ml, 500ug/ml, 1000ug/ml, 2500ug/ml DSPE-PEG-Man @ Fe3O4-Cpds, respectively (FIG. 6).
While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not to be limited to the disclosed embodiment, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (9)
1. A preparation method of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages is characterized by comprising the following steps:
1) Preparing a carbonized polymer dot, weighing 50mg of p-toluenesulfonate, placing in a small bottle, adding polyethylene glycol by using a pipettor, uniformly mixing, transferring the completely mixed solution into a reaction kettle by using the pipettor, placing in an oven, and keeping at 180 ℃ for 8 hours; filtering the reaction product with a 0.22um filter membrane; filling the filtered solution into a 3500 dialysis membrane for dialysis, and changing water every 6 hours for 4-6 times; centrifuging the seeped substances, removing supernatant, putting the obtained solid substances into a drying oven at 60 ℃ for drying for about 2 hours, and collecting solid carbon points to obtain carbonized polymer points;
2) Oleic acid-coated ferroferric oxide, ferrous sulfate and ferric chloride are added into distilled water under the stirring state, and the weight ratio of ferrous sulfate: ferric chloride: distilled water =1: 1:8-12, adding ammonia water 1ml to generate black deposition, and then adding 2ml oleic acid; then, heating to 80 ℃ under the protection of nitrogen at the stirring speed of 300r/min, and reacting for 2 hours; finally, washing the product to be neutral, and drying the product in an oven at the temperature of 60-80 ℃ for 4-6h to obtain Fe coated with oleic acid 3 O 4 Nanoparticles;
3) Adding distearoylphosphatidylethanolamine-polyethylene glycol-D-mannose-coated carbonized polymer dots and ferroferric oxide, taking 5mg of the carbonized polymer dots, taking 40mg of DSPE-PEG-mannose, placing in a 5ml small bottle, adding an organic solution in a fume hood, taking 1ml of oleic acid-coated Fe 3 O 4 Adding the nanoparticles into a small bottle, uniformly mixing the nanoparticles under ultrasonic waves, then adding 50ml of water into a round-bottom flask, adding the uniformly mixed solution onto the liquid level of the round-bottom flask, making the solution out of the sun, placing the solution into a heating stirrer, and stirring the solution at the temperature of 40-80 ℃ and the stirring speed of 550-650 r/min until the organic solution is completely volatilized;
spin-drying the residual solution in the round-bottom flask by using a rotary evaporator to obtain a solid substance; adding 10ml phosphate buffer salt solution for dissolving, collecting by using a 20ml syringe, filtering by using an aqueous phase 0.44um filter, placing in a small bottle for later use, and performing dark preservation by using tinfoil to obtain the photomagnetic bimodal nanoparticles targeting tumor-associated macrophages.
2. The method for preparing the photomagnetic bimodal nanoparticle targeted to tumor-associated macrophages according to claim 1, wherein the photomagnetic bimodal nanoparticle comprises: adding 500mg of ferrous sulfate and 500mg of ferric trichloride into 5ml of distilled water in the step 2) to fully react, adding 1ml of ammonia water to generate black precipitate, and adding 2ml of oleic acid after keeping the temperature constant; according to the weight ratio of ferrous sulfate: ferric chloride: distilled water =1: 1.
3. The method for preparing the photomagnetic bimodal nanoparticle targeted to the tumor-associated macrophages according to claim 1, wherein the photomagnetic bimodal nanoparticle comprises: the Fe coated with oleic acid in the step 3) 3 O 4 The nano particle is 5mg/ml Fe coated with oleic acid 3 O 4 Nanoparticles.
4. The method for preparing the photomagnetic bimodal nanoparticle targeted to the tumor-associated macrophages according to claim 1, wherein the photomagnetic bimodal nanoparticle comprises: the carbonized polymer dots in the step 3) are Fe coated with oleic acid 3 O 4 The mass ratio of the nanoparticles to the DSPE-PEG-mannose is 1:1:8.
5. the method for preparing the photomagnetic bimodal nanoparticle targeted to the tumor-associated macrophages according to claim 1, wherein the photomagnetic bimodal nanoparticle comprises: the organic solvent in the step 3) is one of tetrahydrofuran and toluene.
6. The method for preparing the photomagnetic bimodal nanoparticle targeted to the tumor-associated macrophages according to claim 1, wherein the photomagnetic bimodal nanoparticle comprises: and (3) placing the organic solution in a heating stirrer at the temperature of 60 ℃ and the stirring speed of 600 revolutions until the organic solution is completely volatilized.
7. The method for preparing the photomagnetic bimodal nanoparticle targeted to the tumor-associated macrophages according to claim 1, wherein the photomagnetic bimodal nanoparticle comprises: the nano particles in the step 3) are photomagnetic bimodal nano particles DSPE-PEG-Man @ Fe3O4-Cds.
8. The use of the photomagnetic bimodal nanoparticle DSPE-PEG-Man @ Fe3O4-Cds targeting tumor-associated macrophages of claim 1 for colorectal cancer and metastasis.
9. Use according to claim 1 or 8, characterized in that: the photomagnetic bimodal nanoparticles targeting the tumor-associated macrophages perform non-invasive monitoring on the occurrence, development and outcome of diseases at the cellular and molecular level through nuclear magnetic resonance negative imaging and infrared fluorescence imaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211131148.XA CN115487319A (en) | 2022-09-16 | 2022-09-16 | Preparation method and application of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211131148.XA CN115487319A (en) | 2022-09-16 | 2022-09-16 | Preparation method and application of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115487319A true CN115487319A (en) | 2022-12-20 |
Family
ID=84468790
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211131148.XA Pending CN115487319A (en) | 2022-09-16 | 2022-09-16 | Preparation method and application of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115487319A (en) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105920601A (en) * | 2016-04-21 | 2016-09-07 | 上海工程技术大学 | Folic acid coupled targeted ferriferrous oxide/mesoporous silica/copper sulfide nano-composite particle as well as preparation method and application thereof |
| CN110251688A (en) * | 2019-05-10 | 2019-09-20 | 江苏大学 | A kind of Gd doping carbon dots load Fe3O4The preparation method of multi-modality imaging probe |
| CN110655117A (en) * | 2019-09-30 | 2020-01-07 | 天津大学 | Method for preparing ferroferric oxide with different sizes and good dispersibility |
| CN113385143A (en) * | 2021-04-22 | 2021-09-14 | 华南农业大学 | Magnetic nano carbon dot/ferroferric oxide composite material and preparation method and application thereof |
| WO2022112944A1 (en) * | 2020-11-25 | 2022-06-02 | Università Degli Studi Di Palermo | Nanosystem for diagnosis and photothermal treatment of tumors |
| CN114748424A (en) * | 2020-12-29 | 2022-07-15 | 中国科学院上海药物研究所 | Liposome drug delivery system and preparation method and application thereof |
-
2022
- 2022-09-16 CN CN202211131148.XA patent/CN115487319A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105920601A (en) * | 2016-04-21 | 2016-09-07 | 上海工程技术大学 | Folic acid coupled targeted ferriferrous oxide/mesoporous silica/copper sulfide nano-composite particle as well as preparation method and application thereof |
| CN110251688A (en) * | 2019-05-10 | 2019-09-20 | 江苏大学 | A kind of Gd doping carbon dots load Fe3O4The preparation method of multi-modality imaging probe |
| CN110655117A (en) * | 2019-09-30 | 2020-01-07 | 天津大学 | Method for preparing ferroferric oxide with different sizes and good dispersibility |
| WO2022112944A1 (en) * | 2020-11-25 | 2022-06-02 | Università Degli Studi Di Palermo | Nanosystem for diagnosis and photothermal treatment of tumors |
| CN114748424A (en) * | 2020-12-29 | 2022-07-15 | 中国科学院上海药物研究所 | Liposome drug delivery system and preparation method and application thereof |
| CN113385143A (en) * | 2021-04-22 | 2021-09-14 | 华南农业大学 | Magnetic nano carbon dot/ferroferric oxide composite material and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| DONGDONG WANG 等: "Magnetically guided delivery of DHA and Fe ions for enhanced cancer therapy based on pH-responsive degradation of DHA-loaded Fe3O4@C@MIL-100(Fe) nanoparticles", BIOMATERIALS, vol. 107, 24 August 2016 (2016-08-24), pages 88 - 101, XP029733979, DOI: 10.1016/j.biomaterials.2016.08.039 * |
| 梅雪天: "新型红光及近红外荧光碳化聚合物点的制备及生物成像", 中国优秀硕士学位论文全文数据库 工程科技I辑, no. 01, 15 January 2022 (2022-01-15), pages 014 - 1171 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Dong et al. | Upconversion-mediated ZnFe 2 O 4 nanoplatform for NIR-enhanced chemodynamic and photodynamic therapy | |
| Silva et al. | Gold coated magnetic nanoparticles: from preparation to surface modification for analytical and biomedical applications | |
| Jutz et al. | Ferritin: a versatile building block for bionanotechnology | |
| Wang et al. | Magnetic iron oxide–fluorescent carbon dots integrated nanoparticles for dual-modal imaging, near-infrared light-responsive drug carrier and photothermal therapy | |
| Tada et al. | Methylene blue-containing silica-coated magnetic particles: a potential magnetic carrier for photodynamic therapy | |
| Yin et al. | Recent progress in biomedical applications of titanium dioxide | |
| George et al. | A cast-mold approach to iron oxide and Pt/iron oxide nanocontainers and nanoparticles with a reactive concave surface | |
| Cai et al. | Large-scale, facile transfer of oleic acid-stabilized iron oxide nanoparticles to the aqueous phase for biological applications | |
| Na et al. | Versatile PEG-derivatized phosphine oxide ligands for water-dispersible metal oxide nanocrystals | |
| Bertuit et al. | Structure–property–function relationships of iron oxide multicore nanoflowers in magnetic hyperthermia and photothermia | |
| Khaniabadi et al. | Trastuzumab conjugated porphyrin-superparamagnetic iron oxide nanoparticle: A potential PTT-MRI bimodal agent for herceptin positive breast cancer | |
| Wang et al. | Multifunctional PEG encapsulated Fe 3 O 4@ silver hybrid nanoparticles: antibacterial activity, cell imaging and combined photothermo/chemo-therapy | |
| Liu et al. | One-step shell polymerization of inorganic nanoparticles and their applications in SERS/nonlinear optical imaging, drug delivery and catalysis | |
| MXPA06013095A (en) | Activatable particles, preparations and uses. | |
| CN107381580A (en) | A kind of preparation method of the interior doping metal net shaped Biodegradable silica dioxide granule of polyphenol | |
| Ma et al. | Image-guided selection of Gd@ C-dots as sensitizers to improve radiotherapy of non-small cell lung cancer | |
| Sun et al. | Novel core–shell magnetic nanogels synthesized in an emulsion-free aqueous system under UV irradiation for targeted radiopharmaceutical applications | |
| JP2012513947A (en) | Process for producing processed superparamagnetic magnesium doped ferrite nanoparticles exhibiting high temperature AC magnetic induction heat generation, and processed superparamagnetic magnesium doped ferrite nanoparticles produced by the method | |
| CN101002951A (en) | Superparamagnetism magnetic resonance contrast medium, and its preparing method | |
| Khosroshahi et al. | Characterization and Cellular Fluorescence Microscopy of Superparamagnetic Nanoparticles Functionalized with Third Generation Nano-molecular Dendrimers: In-vitro Cytotoxicity and Uptake study. J Nanomater Mol Nanotechnol 5: 3 | |
| Wotschadlo et al. | Magnetic nanoparticles coated with carboxymethylated polysaccharide shells—Interaction with human cells | |
| KR101779283B1 (en) | Tl-T2 dual-mode magnetic resonance imaging contrast agent | |
| CN115487319A (en) | Preparation method and application of photomagnetic bimodal nanoparticles targeting tumor-associated macrophages | |
| Shabanzadeh-Kouyakhi et al. | Synthesis method of novel Gd2O3@ Fe3O4 nanocomposite modified by dextrose capping agent | |
| Ding et al. | Magnetic upconversion luminescent nanocomposites with small size and strong super-paramagnetism: polyelectrolyte-mediated multimagnetic-beads embedding |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |