CN114933904A - 一种用于光学诊疗的超薄壳层手性硒化镉/硫化镉材料及其制备方法与应用 - Google Patents
一种用于光学诊疗的超薄壳层手性硒化镉/硫化镉材料及其制备方法与应用 Download PDFInfo
- Publication number
- CN114933904A CN114933904A CN202210665350.4A CN202210665350A CN114933904A CN 114933904 A CN114933904 A CN 114933904A CN 202210665350 A CN202210665350 A CN 202210665350A CN 114933904 A CN114933904 A CN 114933904A
- Authority
- CN
- China
- Prior art keywords
- chiral
- cdse
- cds
- cadmium
- drs
- 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.)
- Granted
Links
- 229910052980 cadmium sulfide Inorganic materials 0.000 title claims abstract description 126
- UHYPYGJEEGLRJD-UHFFFAOYSA-N cadmium(2+);selenium(2-) Chemical compound [Se-2].[Cd+2] UHYPYGJEEGLRJD-UHFFFAOYSA-N 0.000 title claims abstract description 90
- WUPHOULIZUERAE-UHFFFAOYSA-N 3-(oxolan-2-yl)propanoic acid Chemical compound OC(=O)CCC1CCCO1 WUPHOULIZUERAE-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 238000011282 treatment Methods 0.000 title abstract description 21
- 238000003745 diagnosis Methods 0.000 title abstract description 14
- 239000000463 material Substances 0.000 title abstract description 11
- 230000003287 optical effect Effects 0.000 title abstract description 8
- 239000002086 nanomaterial Substances 0.000 claims abstract description 43
- 238000002428 photodynamic therapy Methods 0.000 claims abstract description 13
- 239000000126 substance Substances 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 10
- 230000035484 reaction time Effects 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 36
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- 230000005012 migration Effects 0.000 claims description 17
- 238000013508 migration Methods 0.000 claims description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 14
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 239000003446 ligand Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 229910052786 argon Inorganic materials 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 9
- 235000018417 cysteine Nutrition 0.000 claims description 9
- 238000000799 fluorescence microscopy Methods 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 7
- ODJQKYXPKWQWNK-UHFFFAOYSA-N 3,3'-Thiobispropanoic acid Chemical compound OC(=O)CCSCCC(O)=O ODJQKYXPKWQWNK-UHFFFAOYSA-N 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 6
- 239000008213 purified water Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 239000006228 supernatant Substances 0.000 claims description 6
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 206010064390 Tumour invasion Diseases 0.000 claims description 4
- 230000009400 cancer invasion Effects 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 239000012216 imaging agent Substances 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 239000012071 phase Substances 0.000 claims description 4
- 239000012300 argon atmosphere Substances 0.000 claims description 3
- 230000001659 chemokinetic effect Effects 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- MJNSMKHQBIVKHV-UHFFFAOYSA-N selenium;trioctylphosphane Chemical compound [Se].CCCCCCCCP(CCCCCCCC)CCCCCCCC MJNSMKHQBIVKHV-UHFFFAOYSA-N 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims description 2
- 229930195710 D‐cysteine Natural products 0.000 claims description 2
- QIJRTFXNRTXDIP-JIZZDEOASA-N L-cysteine hydrochloride hydrate Chemical compound O.Cl.SC[C@H](N)C(O)=O QIJRTFXNRTXDIP-JIZZDEOASA-N 0.000 claims description 2
- 239000000032 diagnostic agent Substances 0.000 claims description 2
- 229940039227 diagnostic agent Drugs 0.000 claims description 2
- 230000009977 dual effect Effects 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 239000008346 aqueous phase Substances 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 abstract description 16
- 208000032612 Glial tumor Diseases 0.000 abstract description 15
- 239000002096 quantum dot Substances 0.000 abstract description 9
- 238000012984 biological imaging Methods 0.000 abstract description 6
- 238000002347 injection Methods 0.000 abstract description 3
- 239000007924 injection Substances 0.000 abstract description 3
- 239000012620 biological material Substances 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000002114 nanocomposite Substances 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 55
- 230000000694 effects Effects 0.000 description 14
- 239000002105 nanoparticle Substances 0.000 description 13
- 239000003642 reactive oxygen metabolite Substances 0.000 description 13
- 230000009545 invasion Effects 0.000 description 12
- 238000011534 incubation Methods 0.000 description 9
- 239000010410 layer Substances 0.000 description 8
- 238000007619 statistical method Methods 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 229960002433 cysteine Drugs 0.000 description 7
- 210000004881 tumor cell Anatomy 0.000 description 7
- 230000008901 benefit Effects 0.000 description 6
- 238000002983 circular dichroism Methods 0.000 description 6
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 238000012757 fluorescence staining Methods 0.000 description 5
- 239000003504 photosensitizing agent Substances 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- 201000007983 brain glioma Diseases 0.000 description 4
- 229910052793 cadmium Inorganic materials 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 208000003174 Brain Neoplasms Diseases 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- 238000002679 ablation Methods 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000029578 entry into host Effects 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 238000005424 photoluminescence Methods 0.000 description 3
- 238000006862 quantum yield reaction Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 238000003570 cell viability assay Methods 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 238000010835 comparative analysis Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012737 fresh medium Substances 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 238000001126 phototherapy Methods 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000004065 semiconductor Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- VQVUBYASAICPFU-UHFFFAOYSA-N (6'-acetyloxy-2',7'-dichloro-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(Cl)=C(OC(C)=O)C=C1OC1=C2C=C(Cl)C(OC(=O)C)=C1 VQVUBYASAICPFU-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 238000009012 ROS assay kit Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000012200 cell viability kit Methods 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 238000000978 circular dichroism spectroscopy Methods 0.000 description 1
- 238000001142 circular dichroism spectrum Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229960002378 oftasceine Drugs 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 238000000103 photoluminescence spectrum Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- LJPYJRMMPVFEKR-UHFFFAOYSA-N prop-2-ynylurea Chemical compound NC(=O)NCC#C LJPYJRMMPVFEKR-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting 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
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 238000001392 ultraviolet--visible--near infrared spectroscopy Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/88—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing selenium, tellurium or unspecified chalcogen elements
- C09K11/881—Chalcogenides
- C09K11/883—Chalcogenides with zinc or cadmium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/542—Carboxylic acids, e.g. a fatty acid or an amino acid
-
- 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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y20/00—Nanooptics, e.g. quantum optics or photonic crystals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
- C09K11/025—Use of particular materials as binders, particle coatings or suspension media therefor non-luminescent particle coatings or suspension media
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Nanotechnology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Materials Engineering (AREA)
- Physics & Mathematics (AREA)
- Pharmacology & Pharmacy (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Immunology (AREA)
- Optics & Photonics (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Pathology (AREA)
- Analytical Chemistry (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Manufacturing & Machinery (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及纳米生物材料领域,具体涉及一种用于光学诊疗的手性硒化镉/硫化镉及其制备方法与应用。本发明提供了通过控制注入温度和反应时间制备出壳层厚度仅有0.35nm的手性CdSe/CdS DRs。由于其具有优良的点棒状形状,其手性信号比球形CdSe/CdS量子点高10倍,本发明提供的手性硒化镉/硫化镉纳米材料具有多功能性质,各成分比例方便调节,可作为生物成像引导的手性光动力疗法和化学动力疗法材料用于胶质瘤诊疗,具有良好的应用前景。本发明的制备方法通过简单的氧化还原法即可制得该手性纳米复合材料,制备过程简单、绿色环保、成本低廉,具有重要的临床应用和推广价值。
Description
技术领域
本发明涉及纳米生物材料领域,具体涉及一种壳层厚度仅有0.35nm的手性硒化镉/硫化镉点棒状量子点的制备方法、脑胶质瘤光学诊疗及抑制其侵袭转移的用途。
背景技术
光动力疗法(Photodynamic therapy,PDT)是指光敏剂(PSs)在激光的照射下使肿瘤组织产生更多的活性氧(ROS),继而杀死肿瘤细胞的癌症治疗方式。与传统的PSs相比,手性纳米PSs具有尺寸小、亲水性、靶向性强、比表面积大、较高的生物利用度和表面反应活性等优点,成为最有前途的PDT药物。化学动力疗法(Chemodynamic therapy,CDT)则是指由于肿瘤细胞微环境富含H2O2,药物被光激发后产生芬顿效应或类芬顿效应,生成具有强细胞毒性的羟基自由基(·OH),从而杀伤肿瘤细胞。芬顿效应是提高细胞内ROS水平的一种有效途径,其利用Fe(Ⅱ)催化细胞代谢产生的H2O2转化为高毒性强氧化性的·OH。类芬顿效应是除Fe(Ⅱ)以外,Fe(Ⅲ)以及其他一些过渡金属如Co、Cd、Cu、Ag、Mo、Ni等对H2O2具有催化效应的总称。与PDT相比,CDT具有更高效的抗肿瘤生物学效应,由于肿瘤微环境中的内源性化学能触发的CDT可以有效避免对正常组织的氧化损伤,因而具有肿瘤特异性,而且 CDT 既不需要足够的氧气也不需要外部能量输入,这可以防止治疗期间的能量衰减。
具有诱导光学活性的II-VI类镉基量子点被广泛认为是应用于立体催化、3D显示、自旋电子学和生物问题的手性相关诊疗试剂的突破性候选材料,这不仅仅是因为它们的合成方法多样、简便和物理化学稳定性,更重要的是可调的手性吸收/发射特性。其中手性氨基酸配体的引入大大降低了重金属镉的总体生物毒性,并提高了对入射光的选择特性。由于其超小的尺寸和高量子产率的红光发射特性,可以在癌细胞内实现增强的渗透性和保留性(EPR)效应,从而获得高分辨率的荧光成像。在PDT和CDT中,手性硒化镉/硫化镉点棒状纳米粒子(CdSe/CdS DRs)的大小(长径比和壳层厚度)和对映选择性在相当大程度上对活性氧(如1O2)和类芬顿反应产生·OH起至关重要的作用。此外,手性CdSe/CdS DRs可有效避免胶质瘤细胞的浸润性生长和转移,手性CdSe/CdS DRs处理后可明显降低胶质瘤50%的迁移和侵袭能力,为复发性高、预后差的癌症治疗提供了辅助策略。总之,无机量子点具有强而稳定的荧光特性、超小的尺寸、光热转换和光/化学动力学能力等优点,将成为生物成像和双模式治疗的多功能纳米材料。
胶质瘤是最常见的原发性恶性脑肿瘤之一,被认为起源于胶质干细胞或祖细胞。浸润性生长及恶性增殖边界不清的特点是导致其预后极差,发病率和死亡率高的主要原因。脑肿瘤的传统治疗,包括放疗、化疗和手术切除,以及新兴的免疫疗法,这些治疗都面临着不同程度的挑战。脑肿瘤治疗的主要障碍包括脑组织的复杂性、化疗引起的获得性耐药、肿瘤的异质性和侵袭性、难以识别肿瘤组织边缘等。使用新材料、新机制是解决恶性肿瘤的必然趋势,具有多维度的节能型手性功能纳米材料将成为研究的热点。
通过控制注入温度和反应时间,手性CdSe/CdS DRs的壳层厚度仅有0.35nm且应用于胶质瘤的诊疗目前尚无报道。
发明内容
针对上述问题,本发明的第一目的在于受配体诱导的手性优点的驱动,提出新型无机手性半导体纳米材料-壳层厚度仅有0.35nm的手性硒化镉/硫化镉纳米粒子。
本发明的第二目的在于提供所述新型无机手性半导体纳米材料-壳层厚度仅有0.35nm的手性硒化镉/硫化镉纳米粒子的制备方法。
本发明的第三目的在于提供所述壳层厚度仅有0.35nm的手性硒化镉/硫化镉纳米粒子在制备肿瘤生物成像引导的光动力疗法和化学动力疗法诊疗剂中的用途,及其抑制肿瘤侵袭及迁移的作用。
为了实现上述目的,本发明提供了如下技术方案。
一种手性硒化镉/硫化镉纳米材料,其特征在于,所述手性硒化镉/硫化镉纳米材料的壳层厚度为0.35nm,其化学式为L-/D-Cys-CdSe/CdS DRs。
进一步地,所述L-/D-Cys-CdSe/CdS DRs首先通过有机相合成各向异性CdSe/CdSDRs,然后在有机相/水相混合体系中与L/ D-半胱氨酸进行配体交换,得到水溶性的L-/D-Cys-CdSe/CdS DRs。
进一步地,所述手性硒化镉/硫化镉纳米材料在制备肿瘤生物成像引导的光动力疗法和/或化学动力疗法诊疗剂中的用途。
一种荧光成像剂,其特征在于,所述成像剂包括权利要求1所述的手性硒化镉/硫化镉纳米材料。
一种光动力疗法药物,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体。
一种化学动力疗法药物,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体。
一种双模式光疗剂,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体,所述双模式为光动力和化学动力。
一种肿瘤侵袭及迁移抑制剂,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体。
本发明还提供一种如上所述的手性硒化镉/硫化镉纳米材料的制备方法,其特征在于,所述制备方法包括以下步骤:
S1:将TOPO、TDPA、CdO按摩尔比4~40:1.5~8:1的比例搅拌混匀,在150℃加热至CdO为棕色固体、其余试剂为无色后,在真空条件和氩气中交替至少5次,充分除去体系内的水/氧气;然后在氩气下加热至320℃以上,使其充分溶解,直到溶液变得透明无色,然后将温度升高到350℃,向烧瓶中注入4.5mL TOP,使温度自然下降到300℃;然后升温至380℃,加入浓度为1mol/L的Se-TOP溶液1.6mL(Cd:Se摩尔比1:1.2~10),反应5~60秒;
S2:将S1制得溶液冷却至70~80℃后,加入S1溶液1倍体积的有机溶剂和2倍体积乙醇,10000rpm离心3min,弃上清液;将沉淀重新分散于甲苯后,再加入2倍体积的乙醇,10000rpm离心3min,弃上清;沉淀在TOP中重新分散,得到CdSe-TOP溶液;
S3:将CdO、(TDPA+HPA)、TOPO按摩尔比1:1.5~8:4~40混合,在150℃的条件下交替置于真空和氩气中至少5次,然后加热到300℃,使其完全变成透明的液体后,向其中加入TOP,加入的量按照TOP:CdO的摩尔比0.1~20:1,加热至300~320℃后,加入3.0mL浓度为2.5mol/L的S-TOP(S:CdO摩尔比2~20:1)和S2中制得的1mL CdSe-TOP溶液的混合溶液,继续反应6~8分钟,制得CdSe/CdS纳米材料;
S4:将半胱氨酸盐酸—水合物溶于去氧纯净水中配置浓度为0.001 mol/L到0.2mol/L半胱氨酸溶液,用TMAH溶液(AR,25wt.% in H2O)调整pH为6~14;将S3中制得的浓度为7.2mg/mL CdSe/CdS DRs的正己烷溶液添加到上述配置的半胱氨酸溶液,将上述反应混合物在室温氩气气氛下,避光搅拌72h,之后静置1h,使两相分离;底部水层取出后,用Millipore超离心过滤装置(10000d,15mL)将Cys-CdSe/CdS DRs用去氧纯净水离心5次;或利用体积比为1:2~8的水/乙醇体系离心纯化2次,即可制得壳层厚度0.35nm的手性硒化镉/硫化镉纳米材料。
进一步地,所述S1中反应5s时,发射峰560 nm;10s时,发射峰580 nm;30s时,发射峰600 nm;60s时,发射峰615 nm;S2中所述有机溶剂包括甲苯、正己烷,环己烷,三氯甲烷,正庚烷。
与现有技术相比本发明的有益效果。
本发明提供了一种通过手性分子的表面功能化,诱导CdSe/CdS DRs的手性特性以及其固有的优点(超小的尺寸,稳定的荧光特性等),将从根本上扩展其研究更复杂的生物问题的范围。为了定量DRs的CD响应,计算了各向异性g因子,其中g因子的最大值用于指示所诱导的手性的强弱。
本发明提供了通过控制注入温度和反应时间制备出壳层厚度仅有0.35nm的手性CdSe/CdS DRs。由于其具有优良的点棒状形状,其手性信号比球形CdSe/CdS量子点高10倍,这可能是由于其特殊的各向异性形态,在生物检测方面具有潜在的应用价值。 即使经过半胱氨酸配体交换过程,DRs也能保持良好的荧光发射特性。此外,由于其特殊的各向异性形态,CPL的活性也高,其中D-Cys-DRs的活性最高为3.89×10-4。
由于半胱氨酸用量的不同使得该型纳米颗粒表面的手性配体的量也会不同,这种不同之处可以通过圆二色谱(CD)进行光谱分析,为该型材料的制备提供了简单便捷的观测方法。此外,本发明中所涉及的Metal-ligand的手性引入概念也可以通过圆二色谱以及紫外可见光谱来跟踪测量,为手性的引入机理提供了理论分析条件。
本发明提供的手性硒化镉/硫化镉纳米材料本身具备高对比度的生物成像光敏剂的效果,由于颗粒小,易于进入肿瘤细胞并滞留。同时手性的引入大大降低重金属镉的生物毒性,具有良好的生物相容性。
本发明提供的手性硒化镉/硫化镉纳米材料具备光动力和化学动力效应结合的双模式光疗剂的效果。其中ROS的生成依赖于手性,D-DRs在右旋手性光源照射(473 nm)下产生的ROS水平是未处理组的3.14倍。并且手性硒化镉/硫化镉纳米材料在对应的手性光源(473 nm)激光照射下产生明显的类芬顿反应。
本发明提供的手性硒化镉/硫化镉纳米材料可有效降低胶质瘤细胞的迁移和侵袭能力近50%。
因此,本发明提供的手性硒化镉/硫化镉纳米材料非常适合用于制备脑胶质瘤诊疗剂。该肿瘤诊疗剂可以用作生物成像的诊断应用,还可以因具有光/化学动力学能力,对胶质瘤细胞提供协同治疗,同时有效避免胶质瘤细胞的浸润性生长和转移,为复发性高、预后差的癌症治疗提供了辅助策略。
综上所述,本发明提供的手性硒化镉/硫化镉纳米材料具有多功能性质,各成分比例方便调节,可作为生物成像引导的手性光动力疗法和化学动力疗法材料用于胶质瘤诊疗,具有良好的应用前景。本发明的制备方法通过简单的氧化还原法即可制得该手性纳米复合材料,制备过程简单、绿色环保、成本经济普适。
附图说明
图1为实施例1制备出的手性硒化镉/硫化镉纳米材料的物理性质图,其中A为透射电子显微镜图,B为紫外吸收光谱图,C为CD光谱图,D为DC光谱图,E为CPL镜像光谱图,F为glum因子图。
图2为实施例1不同条件下制备的不同壳层厚度(0.35nm样品命名为DR-1;1.45nm样品命名为DR-2)手性硒化镉/硫化镉纳米材料的荧光成像情况对比图,B为不同壳层厚度的D-CdSe/CdS DRs和 L-CdSe/CdS DRs平均荧光强度的比较分析。壳层厚度超过1.45nm后,粒径及长径比均会增大,影响材料入胞效率及成像质量,降低生物应用价值。
图3为实施例2中手性CdSe/CdS DRs细胞毒性评价图,其中A为荧光显微镜拍摄不同浓度的D-CdSe/CdS纳米颗粒在分别与正常人星形胶质细胞NHA、人胶质瘤细胞U251和U87孵育24小时后的细胞死活荧光染色情况图(标尺:100 µm),B为荧光显微镜拍摄不同浓度的L-CdSe/CdS纳米颗粒在分别与NHA、U251和U87孵育24小时后的细胞死活荧光染色情况图(标尺:100 µm),C和D分别为图A和图B的细胞活力统计分析图。
图4为实施例3中手性CdSe/CdS DRs在U251中的荧光成像情况图,其中A为不同浓度的手性CdSe/CdS DRs的荧光成像图(标尺:100 µm),B为图A的荧光强度统计分析图,C为D-CdSe/CdS DRs和 L-CdSe/CdS DRs(50 μg/mL)平均荧光强度的比较分析。
图5为实施例4中手性CdSe/CdS DRs的光动力和化学动力疗法实验图,其中A为手性CdSe/CdS材料在473nm LCP (左旋光)、LP(线偏振光)及RCP(右旋光)照射后(0.5 W/cm2,20 min)U251细胞中ROS的产生情况图(标尺:100 µm),B为图A的ROS荧光强度统计分析图,C为同手性光源照射下,D-CdSe/CdS DRs和 L-CdSe/CdS DRs产生的ROS平均荧光强度的比较分析图,D为手性CdSe/CdS纳米材料在对应的同手性光源照射下的化学动力疗法情况图。
图6为实施例5中手性CdSe/CdS DRs在473 nm激光照射下肿瘤细胞消融实验图,其中A为荧光显微镜拍摄U251在与壳层厚度为0.35nm的L-及D-Cys-CdSe/CdS纳米颗粒(30 μg/mL)共孵育24小时后在473nm LCP、LP及RCP照射后(0.5 W/cm2,30 min)细胞死活荧光染色情况图(标尺:100 µm),B为荧光显微镜拍摄U87在与手性CdSe/CdS纳米颗粒(30 μg/mL)共孵育24小时后在473nm LCP、LP及RCP照射后(0.5 W/cm2,30 min)细胞死活荧光染色情况图(标尺:100 µm),C为图A和B体外消融实验中存活比率统计分析图,图D 为壳层厚度为1.45nm的L-及D-Cys-CdSe/CdS纳米颗粒(30 μg/mL)共孵育24小时后在473nm LCP、LP及RCP照射后(0.5 W/cm2,30 min)细胞死活荧光染色情况图,结果表示壳层过后,同样治疗条件下不能使胶质瘤细胞完全死亡。
图7为实施例6中手性CdSe/CdS DRs抑制胶质瘤细胞的迁移和侵袭能力情况图,其中A为用细胞划痕实验检测D-和L- Cys-CdSe/CdS DRs(30μg/mL)预处理24h后的U251细胞的迁移能力图(标尺:250 µm),B为图A迁移能力的统计分析图,C为Transwell迁移和侵袭实验的示意图,D为通过Transwell分析D-和L- Cys-CdSe/CdS DRs(30 μg/mL)预处理24h后的U251细胞进行二维迁移和侵袭实验的情况图(标尺:100 µm),E和F分别为图D迁移和侵袭能力的统计分析图。
图8为超薄壳层手性硒化镉/硫化镉纳米材料诊疗模式图。
具体实施方式
下面通过实施例对本发明进行详细说明,以使本发明的特征和优点更清楚。但应该指出,实施例用于理解本发明的构思,本发明的范围并不仅仅局限于本文中所列出的实施例。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1。
S1:将TOPO、TDPA、CdO按摩尔比20:2:1的比例搅拌混匀,在150℃加热至CdO为棕色固体、其余试剂为无色后,在真空条件和氩气中交替至少5次,充分除去体系内的水/氧气;然后在氩气下加热至320℃以上,使其充分溶解,直到溶液变得透明无色,然后将温度升高到350℃,向烧瓶中注入4.5mL TOP,使温度自然下降到300℃;然后升温至380℃,加入浓度为1mol/L的Se-TOP(Cd:Se摩尔比1:1.6)溶液1.6mL,反应5~60秒。
S2:将S1制得溶液冷却至70~80℃后,加入S1溶液1倍体积的有机溶剂和2倍体积乙醇,10000rpm离心3min,弃上清液;将沉淀重新分散于甲苯后,再加入2倍体积的乙醇,10000rpm离心3min,弃上清;沉淀在TOP中重新分散,得到CdSe-TOP溶液。
S3:将CdO、TDPA、HPA、TOPO按摩尔比1:2:1:20混合,在150℃的条件下交替置于真空和氩气中至少5次,然后加热到300℃,使其完全变成透明的液体后,向其中加入TOP,加入的量按照TOP:CdO的摩尔比10:1,加热至320℃后,加入3.0mL浓度为2.5mol/L的S-TOP(S:CdO摩尔比8:1)和S2中制得的2mL CdSe-TOP溶液的混合溶液,继续反应8分钟,制得CdSe/CdS纳米材料。
S4:将0.1mol/L半胱氨酸盐酸一水化物溶于去氧纯净水中,用TMAH溶液(AR,25wt.% in H2O)调整pH为12;将S3中制得的浓度为7.2mg/mL CdSe/CdS DRs的正己烷溶液5mL添加到上述配置的半胱氨酸溶液(5mL),将上述反应混合物在室温氩气气氛下,避光搅拌72h,之后静置1h,使两相分离;底部水层取出后,用Millipore超离心过滤装置(10000d,15mL)将Cys-CdSe/CdS DRs用去氧纯净水离心5次,或利用体积比为1:2~8的水/乙醇体系离心纯化2次,即可制得壳层厚度0.35nm的手性硒化镉/硫化镉纳米材料。
半胱氨酸浓度增大,pH增大,可以加速配体交换速度;但是浓度增大,pH增大,会使得后续纯化过程变得更复杂。综合考虑了不同的浓度、不同pH对配体交换速度的影响,以及手性溶液后处理复杂程度的影响。选择了大浓度(0.1 M),较高pH 12的半胱氨酸前驱体进行配体交换反应。
此后,手性样品的样品颗粒的形貌由Tecnai F30 透射电子显微镜测定,吸收光谱由TU-1901 双光紫外-可见光谱仪测定,圆二色谱(CD)则由 JASCO J-1500 CD光谱仪测定表征,CPL光谱由JASCO cpl300光谱仪测定,光致发光光谱(PL)由fluoroSENS分光光度计(Gilden Photonics)测定。
实施例2。
使用活细胞/死细胞活力检测试剂盒(美国,Invitrogen公司),根据制造商说明进行活细胞/死细胞活力测定。首先将约1.2×104个细胞/孔接种于96孔板,培养过夜,使细胞80-90%融合。然后新鲜的培养基与不同浓度的纳米晶体混合后加入并继续培养24小时。之后,细胞被1×PBS洗两次后加入100 µL的2×10−6 M钙黄绿素和4×10−6 M EthD-1的混合物避光室温下孵育45分钟。孵育后用1× PBS避光冲洗2次,最后用Olympus IX71荧光显微镜(东京,日本)拍照。
图2为实施例2中手性CdSe/CdS DRs细胞毒性评价图,在进行生物医学研究之前,对其在NHA、U251和U87细胞系中的细胞毒性进行了评估。在细胞中加入0 ~ 125 µg/mL的Cys-CdSe/CdS DRs,孵育24 h后,D-/L-Cys-CdSe/CdS DRs 在50 µg/mL浓度时细胞活力均能保持在90%以上,100 µg/mL时细胞活力仍能保持在80%以上。此外,D-/L-Cys-CdSe/CdSDRs对正常细胞的毒性均较低,可达75 µg/mL。这些结果表明,手性半胱氨酸配体可明显降低Cd基纳米颗粒的细胞毒性,提高其生物相容性,促进其在生物领域的应用。此外,细胞活力检测表明,L-Cys-CdSe/CdS DRs比D-Cys-CdSe/CdS DRs表现出更好的生物相容性,这可能是由于细胞膜对手性分子的选择性亲和力。
利用球形的CdSe/ZnS核壳量子点作为CdSe/CdS DRs的替代,由于球形CdSe/ZnS各向同性的球形结构以及厚壳层,其手性信号低于量子棒结构(只有其10%)。使得测试灵敏度急剧降低,无法分辨出手性激光信号。
实施例3。
约1.5×105个U251细胞/孔种到含14 mm爬片的24孔板中培养24 h。随后,不同浓度的CdSe/CdS DRs添加到细胞中继续培养24 h。然后,这些细胞被4%多聚甲醛固定后细胞核染DAPI(Solarbio,中国)。细胞成像用倒置共聚焦显微镜(Nikon,美国)进行拍摄分析。
图3为实施例3中手性CdSe/CdS DRs在U251中的荧光成像情况图,结果显示荧光强度随DRs的浓度呈剂量依赖性增加。在30 μg/mL以上,细胞发出明亮的深红色光,表明L-/D-CdSe/CdS DRs具有较高的光致发光(PL)量子产率(QY),且在细胞质中分布均匀。此外,可以明显看到D-Cys-CdSe/CdS DRs的荧光成像性能优于L-Cys-CdSe/CdS DRs。
实施例4。
将细胞种于上述24孔板中,加入30 μg/mL CdSe/CdS DRs孵育24h。然后用473 nm,0.5 W/cm2的激光照射细胞20分钟后将细胞置于培养箱中继续生长5小时。采用活性氧检测试剂盒(Beyotime,中国)测定ROS。用10 μM探针2',7'-二氯荧光素双乙酸酯(DCFH-DA)在不含胎牛血清的DMEM培养基中37℃孵育30分钟。4%多聚甲醛固定细胞,DAPI染色。倒置共聚焦显微镜下观察细胞内ROS水平。
取100 μg/mL手性CdSe/CdS DRs、1 mM OPDA和1 mM H2O2(其余加ddH2O)的混合物3mL,用相应的手性光源照射15 min(473 nm,0.5 W/cm2),测定紫外光谱。
图4为实施例4中手性CdSe/CdS DRs的光动力和化学动力疗法实验图,在不同CPL照射下,RCP处理的D-DRs比LCP处理的L-DRs荧光强,表明ROS的生成依赖于手性。值得注意的是,D-DRs +RCP产生的ROS水平是未处理组的3.14倍。绿色荧光统计分析图显示,在相同处理条件下,D-DRs + RCP相对于L-DRs + LCP,始终表现出更高的ROS生成,这与之前的荧光成像研究一致。•OH是一种高活性的化学物质,可以氧化邻苯二胺(OPDA),将无色的OPDA转化为黄色产物。手性CdSe/CdS DRs在H2O2存在下催化H2O2生成•OH,并进一步氧化OPDA,通过紫外-可见-近红外光谱进行表征。可以看出CPL激光照射下,D-/L- CdSe/CdS DRs在415nm处的特征吸收峰明显,表明该体系中存在类芬顿反应,这表明手性CdSe/CdS DRs可作为化学动力和光动力效应结合的双模式光疗剂。
实施例5。
首先将U251和U87细胞以1.2×104细胞/孔的密度种在96孔板培养24后进一步与30 μg/mL的纳米颗粒孵育另一个24小时。然后激光辐射(473 nm,0.5 W/cm2)30分钟后更换新鲜培养液,将细胞置于培养箱过夜。最后用活细胞/死细胞活力检测试剂盒进行孵育45分钟后荧光显微镜拍摄。
图5为实施例5中手性CdSe/CdS DRs在473 nm激光照射下肿瘤细胞消融实验图,可见RCP处理的D-Cys-CdSe/CdS、LCP处理的L-Cys-CdSe/CdS均能在短时间内显著杀灭几乎所有肿瘤细胞。D-Cys-CdSe/CdS和L-Cys-CdSe/CdS对LCP和RCP激光的敏感性较低,这也证实了L-/D-Cys-CdSe/CdS具有较强的手性选择性吸收。
实施例6。
为了评估手性D-/L-Cys-CdSe/CdS DRs对胶质瘤细胞迁移和侵袭能力的影响,将胶质瘤细胞(6×105)接种到6孔培养板中,直到单层细胞几乎融合。用100 μL无菌移液管枪头均匀划破细胞。用PBS洗涤细胞三次,在光学显微镜(Nikon Ts2,日本)下拍照。然后将划破的单层细胞加入新鲜培养基和D-/L-Cys-CdSe/CdS的混合液中,24小时后再次拍照。
胶质瘤细胞接种于孔径为0.8 μm的Transwell Boyden小室(美国康宁公司)。简单地说,为了进行迁移实验,将细胞接种到6孔培养板中,然后加入D-/L-Cys-CdSe/CdS DRs培养24小时。然后消化并收集和离心细胞。再用PBS重悬细胞,洗涤2次。进行细胞计数,细胞密度调整为3×104/孔。然后,将细胞接种在含2% FBS培养基的上腔中。将含有20% FBS的培养基添加到下腔中作为趋化剂。37℃孵育24 h后,4%多聚甲醛固定迁移细胞,1%结晶紫染色(Coolaber,中国)染色并拍照。侵袭实验采用50 μL基质凝胶(ABW,中国)包裹Boyden小室。基质与DMEM的比例为1∶5。将细胞(1.2×105)与制备的30 μg/mL DRs置于小室,48 h后观察细胞的侵袭能力。其余操作与迁移操作相同。
图6为实施例6中手性CdSe/CdS DRs抑制胶质瘤细胞的迁移和侵袭能力情况图,结果充分证实了手性CdSe/CdS DRs可有效降低胶质瘤细胞的迁移和侵袭能力近50%。
Claims (10)
1.一种手性硒化镉/硫化镉纳米材料,其特征在于,所述手性硒化镉/硫化镉纳米材料的壳层厚度为0.35nm,其化学式为L-/D-Cys-CdSe/CdS DRs。
2.根据权利要求1所述的一种手性硒化镉/硫化镉纳米材料,其特征在于,所述L-/D-Cys-CdSe/CdS DRs首先通过有机相合成各向异性CdSe/CdS DRs,然后与L/D-半胱氨酸进行配体交换,得到水相的L-/D-Cys-CdSe/CdS DRs。
3.根据权利要求1所述的一种手性硒化镉/硫化镉纳米材料在制备肿瘤生物成像引导的光动力疗法和/或化学动力疗法诊疗剂,及肿瘤侵袭及迁移抑制剂中的用途。
4.一种荧光成像剂,其特征在于,所述成像剂包括权利要求1所述的手性硒化镉/硫化镉纳米材料。
5.一种光动力疗法药物,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体。
6.一种化学动力疗法药物,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体。
7.一种双模式光疗剂,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体,所述双模式为光动力和化学动力。
8.一种肿瘤侵袭及迁移抑制剂,其特征在于,所述药物包括权利要求1所述的手性硒化镉/硫化镉纳米材料和/或其他药学上可接受的载体。
9.一种如权利要求1所述的手性硒化镉/硫化镉纳米材料的制备方法,其特征在于,所述制备方法包括以下步骤:
S1:将TOPO、TDPA、CdO按摩尔比4~40:1.5~8:1的比例搅拌混匀,在150℃加热至CdO为棕色固体、其余试剂为无色后,在真空条件和氩气中交替至少5次,充分除去体系内的水/氧气;然后在氩气下加热至320℃以上,使其充分溶解,直到溶液变得透明无色,然后将温度升高到350℃,向烧瓶中注入4.5mL TOP,使温度自然下降到300℃;然后升温至380℃,加入浓度为1mol/L的Se-TOP溶液1.6mL(Cd:Se摩尔比1:1.2~10),反应5~60秒;
S2:将S1制得溶液冷却至70~80℃后,加入S1溶液1倍体积的有机溶剂和2倍体积乙醇,10000rpm离心3min,弃上清液;将沉淀重新分散于甲苯后,再加入2倍体积的乙醇,10000rpm离心3min,弃上清;沉淀在TOP中重新分散,得到CdSe-TOP溶液;
S3:将CdO、(TDPA+HPA)、TOPO按摩尔比1:1.5~8:4~40混合,在150℃的条件下交替置于真空和氩气中至少5次,然后加热到300℃,使其完全变成透明的液体后,向其中加入TOP,加入的量按照TOP:CdO的摩尔比0.1~20:1,加热至300~320℃后,加入3.0mL浓度为2.5mol/L的S-TOP(S:CdO摩尔比2~20:1)和S2中制得的1mL CdSe-TOP溶液的混合溶液,继续反应6~8分钟,制得CdSe/CdS纳米材料;
S4:将半胱氨酸盐酸—水合物溶于去氧纯净水中配置浓度为0.001 mol/L到0.2 mol/L半胱氨酸溶液,用TMAH溶液(AR,25wt.% in H2O)调整pH为6~14;将S3中制得的浓度为7.2mg/mL CdSe/CdS DRs的正己烷溶液添加到上述配置的半胱氨酸溶液,将上述反应混合物在室温氩气气氛下,避光搅拌72h,之后静置1h,使两相分离;底部水层取出后,用Millipore超离心过滤装置(10000d,15mL)将Cys-CdSe/CdS DRs用去氧纯净水离心5次;或利用体积比为1:2~8的水/乙醇体系离心纯化2次,即可制得壳层厚度0.35nm的手性硒化镉/硫化镉纳米材料。
10.根据权利要求9所述的制备方法,其特征在于,所述S1中反应5s时,发射峰560 nm;10s时,发射峰580 nm;30s时,发射峰600 nm;60s时,发射峰615 nm;S2中所述有机溶剂包括甲苯、正己烷,环己烷,三氯甲烷,正庚烷。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210665350.4A CN114933904B (zh) | 2022-06-14 | 2022-06-14 | 一种用于光学诊疗的超薄壳层手性硒化镉/硫化镉材料及其制备方法与应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210665350.4A CN114933904B (zh) | 2022-06-14 | 2022-06-14 | 一种用于光学诊疗的超薄壳层手性硒化镉/硫化镉材料及其制备方法与应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114933904A true CN114933904A (zh) | 2022-08-23 |
CN114933904B CN114933904B (zh) | 2024-02-06 |
Family
ID=82865926
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210665350.4A Active CN114933904B (zh) | 2022-06-14 | 2022-06-14 | 一种用于光学诊疗的超薄壳层手性硒化镉/硫化镉材料及其制备方法与应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114933904B (zh) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20110000524A (ko) * | 2009-06-26 | 2011-01-03 | 주식회사 진코스 | 양자점-클로린 유도체의 접합체를 함유하는 광감작제 및 이를 포함하는 광역학 치료에 사용하기 위한 암 치료 및 진단용 조성물 |
CN112675304A (zh) * | 2021-01-13 | 2021-04-20 | 北京工业大学 | 一种微纳量子点的内源性光热治疗器件系统及其制备方法 |
-
2022
- 2022-06-14 CN CN202210665350.4A patent/CN114933904B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20110000524A (ko) * | 2009-06-26 | 2011-01-03 | 주식회사 진코스 | 양자점-클로린 유도체의 접합체를 함유하는 광감작제 및 이를 포함하는 광역학 치료에 사용하기 위한 암 치료 및 진단용 조성물 |
CN112675304A (zh) * | 2021-01-13 | 2021-04-20 | 北京工业大学 | 一种微纳量子点的内源性光热治疗器件系统及其制备方法 |
AU2021106491A4 (en) * | 2021-01-13 | 2021-11-04 | Beijing University Of Technology | An endogenous photothermal therapy device system of micro-nano quantum dots and its preparation method |
Non-Patent Citations (5)
Title |
---|
FINN PURCELL-MILTON,ETC: "Impact of Shell Thickness on Photoluminescence and Optical Activity in Chiral CdSe/CdS Core/Shell Quantum Dots" * |
J. JACK L,ETC: "Large-Scale Synthesis of Nearly Monodisperse CdSe/CdS Core/Shell Nanocrystals Using Air-Stable Reagents via Successive Ion Layer Adsorption and Reaction" * |
JIAJI CHENG,ETC: "Optically Active CdSe-Dot/CdS-Rod Nanocrystals with Induced Chirality and Circularly Polarized Luminescence" * |
TINGCHAO HE,ETC: "Water-soluble chiral CdSe/CdS dot/rod nanocrystals for two-photon fluorescence lifetime imaging and photodynamic therapy" * |
安娜,等: "CdSe/CdS 核壳量子点复合材料合成及其在白光发光二极管中的应用" * |
Also Published As
Publication number | Publication date |
---|---|
CN114933904B (zh) | 2024-02-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Tang et al. | An aza-BODIPY photosensitizer for photoacoustic and photothermal imaging guided dual modal cancer phototherapy | |
Xu et al. | Combination of CuS and g-C3N4 QDs on upconversion nanoparticles for targeted photothermal and photodynamic cancer therapy | |
LeCroy et al. | Functionalized carbon nanoparticles: syntheses and applications in optical bioimaging and energy conversion | |
Liu et al. | NIR‐triggered anticancer drug delivery by upconverting nanoparticles with integrated azobenzene‐modified mesoporous silica | |
CN109602919B (zh) | 一种核壳金属有机框架包覆的黑磷量子点及其制备方法与应用 | |
Song et al. | Upconversion system with quantum dots as sensitizer: improved photoluminescence and PDT efficiency | |
CN109568578B (zh) | 天然生物质量子点和生物质量子点-铜纳米复合物的制备方法及其应用 | |
NL2026426B1 (en) | Fluorine-containing graphene quantum dots, preparation method and application thereof as photosensitiser for photodanamic therapy | |
Liang et al. | A supramolecular nanovehicle toward systematic, targeted cancer and tumor therapy | |
CN111603559B (zh) | 铜碘簇化合物@光敏剂复合纳米颗粒及其作为x射线光动力治疗药物的应用 | |
Xia et al. | Near-infrared organic fluorescent nanoparticles for long-term monitoring and photodynamic therapy of cancer | |
Xia et al. | Enhanced photodynamic therapy through supramolecular photosensitizers with an adamantyl-functionalized porphyrin and a cyclodextrin dimer | |
Rui et al. | Recent advances in carbon dots-based nanoplatforms: Physicochemical properties and biomedical applications | |
Kang et al. | Applications of nanocomposites based on zeolitic imidazolate framework-8 in photodynamic and synergistic anti-tumor therapy | |
CN113230401A (zh) | 一种核壳上转换MOFs光敏复合材料、制备方法及其应用 | |
CN110743013B (zh) | 用于双动力协同治疗的上转换纳米复合材料、制备方法及应用 | |
CN115385861B (zh) | 一种荧光探针及其制备方法和应用 | |
CN108421040B (zh) | 兼具双光子成像和光动力疗效的共轭高分子的纳米光敏材料及制备与应用 | |
CN114933904B (zh) | 一种用于光学诊疗的超薄壳层手性硒化镉/硫化镉材料及其制备方法与应用 | |
CN107998393B (zh) | 增强光吸收的黑色素/Ce6光动力纳米肿瘤药物及其制备和应用 | |
JP2021528482A (ja) | オキサジン系化合物およびその使用 | |
CN112939905B (zh) | 一种具有聚集诱导发光性质的化合物及其制备方法和应用 | |
CN110642865B (zh) | 一种高电荷阳离子卟啉在制备pdt纳米光敏剂中的应用 | |
CN114601925A (zh) | 透明质酸与rsl3共同修饰的光敏纳米材料、制备方法及其应用 | |
CN108421041B (zh) | 一种光动力治疗复合物及其制备方法与应用 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant | ||
TR01 | Transfer of patent right |
Effective date of registration: 20240621 Address after: No.102, 1st Floor, No.15-1 Feiyun Road, Hunnan District, Shenyang City, Liaoning Province, 110000 Patentee after: Shenyang Qiantan Technology Co.,Ltd. Country or region after: China Address before: 110122 No. 77 Puhe Road, Shenbei New District, Shenyang City, Liaoning Province Patentee before: CHINA MEDICAL University Country or region before: China |