CN113230419A - 一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法 - Google Patents
一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法 Download PDFInfo
- Publication number
- CN113230419A CN113230419A CN202110532361.0A CN202110532361A CN113230419A CN 113230419 A CN113230419 A CN 113230419A CN 202110532361 A CN202110532361 A CN 202110532361A CN 113230419 A CN113230419 A CN 113230419A
- Authority
- CN
- China
- Prior art keywords
- solution
- phycocyanobilin
- novel targeted
- preparation
- phycocyanin
- 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 50
- INPDFIMLLXXDOQ-UHFFFAOYSA-N Phycocyanobilin Natural products CCC1=C(C)C(=CC2=NC(=C/c3[nH]c(C=C/4C(C(C(N4)=O)C)=CC)c(C)c3CCC(=O)O)C(=C2C)CCC(=O)O)NC1=O INPDFIMLLXXDOQ-UHFFFAOYSA-N 0.000 title claims abstract description 41
- NNMALANKTSRILL-ZUTFDUMMSA-N 3-[(2z,5z)-2-[[3-(2-carboxyethyl)-5-[(z)-[(3z,4r)-3-ethylidene-4-methyl-5-oxopyrrolidin-2-ylidene]methyl]-4-methyl-1h-pyrrol-2-yl]methylidene]-5-[(4-ethyl-3-methyl-5-oxopyrrol-2-yl)methylidene]-4-methylpyrrol-3-yl]propanoic acid Chemical compound O=C1C(CC)=C(C)C(\C=C/2C(=C(CCC(O)=O)C(=C/C3=C(C(C)=C(\C=C/4\C(\[C@@H](C)C(=O)N\4)=C/C)N3)CCC(O)=O)/N\2)C)=N1 NNMALANKTSRILL-ZUTFDUMMSA-N 0.000 title claims abstract description 24
- 108010072011 phycocyanobilin Proteins 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 54
- 108010053210 Phycocyanin Proteins 0.000 claims abstract description 34
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 27
- 239000002245 particle Substances 0.000 claims abstract description 18
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 13
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims abstract description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229920002674 hyaluronan Polymers 0.000 claims abstract description 11
- 229960003160 hyaluronic acid Drugs 0.000 claims abstract description 11
- 238000003760 magnetic stirring Methods 0.000 claims abstract description 9
- 238000004108 freeze drying Methods 0.000 claims abstract description 7
- 238000005406 washing Methods 0.000 claims abstract description 7
- 239000002244 precipitate Substances 0.000 claims abstract description 6
- 230000001376 precipitating effect Effects 0.000 claims abstract description 6
- 238000003260 vortexing Methods 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 46
- 239000007853 buffer solution Substances 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 238000001126 phototherapy Methods 0.000 claims description 4
- 238000005119 centrifugation Methods 0.000 claims description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 3
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 3
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 3
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 3
- 239000001103 potassium chloride Substances 0.000 claims description 3
- 235000011164 potassium chloride Nutrition 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 abstract description 7
- 230000008685 targeting Effects 0.000 abstract description 7
- 239000000463 material Substances 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 10
- 210000004881 tumor cell Anatomy 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 5
- 208000026310 Breast neoplasm Diseases 0.000 description 5
- 230000035508 accumulation Effects 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 231100000419 toxicity Toxicity 0.000 description 5
- 230000001988 toxicity Effects 0.000 description 5
- 206010034972 Photosensitivity reaction Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000001678 irradiating effect Effects 0.000 description 4
- 208000007578 phototoxic dermatitis Diseases 0.000 description 4
- 231100000018 phototoxicity Toxicity 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 235000016425 Arthrospira platensis Nutrition 0.000 description 3
- 240000002900 Arthrospira platensis Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 238000002428 photodynamic therapy Methods 0.000 description 3
- 239000003642 reactive oxygen metabolite Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 229940082787 spirulina Drugs 0.000 description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 230000002165 photosensitisation Effects 0.000 description 2
- 108060006184 phycobiliprotein Proteins 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 108010083590 Apoproteins Proteins 0.000 description 1
- 102000006410 Apoproteins Human genes 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229910008051 Si-OH Inorganic materials 0.000 description 1
- 229910006358 Si—OH Inorganic materials 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000001055 blue pigment Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022534 cell killing Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000009513 drug distribution Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000013335 mesoporous material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000006552 photochemical reaction Methods 0.000 description 1
- 231100000119 phototoxicity / photoirritation testing Toxicity 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000036326 tumor accumulation Effects 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Images
Classifications
-
- 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
- A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
- A61K47/6939—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
-
- 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- 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
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Nanotechnology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Crystallography & Structural Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法。该制备方法步骤包括:在磁力搅拌下,向介孔二氧化硅颗粒溶液中加入藻蓝素溶液;室温搅拌24h;离心、沉淀后,加入至含有透明质酸的水中,涡旋2h;再加EDC,涡旋2h,水洗离心三次,所得沉淀冷冻干燥即得新型靶向纳米颗粒。这一新型靶向纳米颗粒作为光敏剂递送系统能够增强癌细胞对水溶性差的藻蓝胆素的稳定性和摄入,增加生物利用度。
Description
技术领域
本发明涉及新材料技术领域,具体涉及一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法。
背景技术
深蓝色的开环四吡咯结构的色基—藻蓝胆素(以下简称PCB)和脱辅基蛋白以硫醚键共价结合而成构成藻蓝蛋白。正是由于PCB的存在,藻蓝蛋白才能通过非放射性过程将激发能高效的向光反应中心传递。
来源于螺旋藻的藻蓝蛋白是目前商业化制备工艺最成熟、制备规模最大的藻胆蛋白,我国通过螺旋藻大规模生产的藻蓝蛋白(以下简称PC),总生产能力约为40吨/年,PCB色基能够占藻胆蛋白干重的1%,因此可以通过甲醇回流法裂解提取足够数量的PCB。作为一种纯天然的蓝色素,市场上缺乏基于PCB的高附加值产品。只是在食品、化妆品中有一定的应用。近来研究发现其具有抗氧化、抗病毒、抗肿瘤、增强免疫力和抗炎作用,尤其是PCB色基具有光学活性可以用于诊断和免疫方面的医学研究,在可见光区680纳米处有强吸收,光照后能够产生活性氧进而应用于肿瘤光动力学治疗,能使选择性聚集在肿瘤组织的光敏药物活化,引发光化学反应破坏肿瘤。PCB吸收光能后会将能量传递给周围的氧分子,生成活性很强的单线态氧;单线态氧能够氧化与附近的生物大分子发生反应,产生细胞毒性进而杀伤肿瘤细胞,引起肿瘤细胞凋亡。同时还具有抑制肿瘤生长的作用,能够通过多方面的共同作用从而达到治疗肿瘤的目的。
现有技术中,来源于螺旋藻的PCB作为一种新型光敏剂,直接给药应用于光动力治疗还受到一些限制,如疏水性的PCB色基容易聚集在生理溶液中,生物相容性较差且分布不均,导致光动力疗法效率的降低。另外,还面临正常组织器官的非特异性摄取、非肿瘤选择性的药物分布、肿瘤积累量不足等问题。
发明内容
针对上述现有技术的不足,本发明提供一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法。该纳米颗粒的稳定性强,靶向性强。
本发明提供一种基于藻蓝胆素的新型靶向纳米颗粒的制备方法,步骤包括:
在磁力搅拌下,向介孔二氧化硅颗粒溶液中加入藻蓝素溶液;室温搅拌24h,离心、沉淀后,加入到含有透明质酸的水中,涡旋2h;再加EDC,涡旋2h,水洗离心三次,所得沉淀冷冻干燥即得新型靶向纳米颗粒。
进一步的,所述离心条件为:12000rpm,30min,4℃。
进一步的,所述藻蓝胆素溶液的配制方法为:将提取的藻蓝素溶解于pH值为6.0-7.4的PBS缓冲液中,得到浓度为5mg/mL的藻蓝素溶液;所述PBS缓冲液的配方为:氯化钠,8g/L;氯化钾,0.2g/L;磷酸氢二钠,1.44g/L;磷酸二氢钾,0.24g/L。
进一步的,所述介孔二氧化硅纳米颗粒溶液的配制方法为:介孔二氧化硅纳米颗粒超声分散到40ml的10X PBS缓冲液中,超声混匀2h,得到介孔二氧化硅颗粒溶液。
本发明还提供一种基于藻蓝胆素的新型靶向纳米颗粒,采用上述的制备方法制备得到。
本发明还提供一种基于藻蓝胆素的新型靶向纳米颗粒的应用,所述新型靶向纳米颗粒在作为光疗治瘤用光敏剂的应用。
为实现上述目的,本发明的技术方案为:
有益效果:本发明通过光敏剂藻蓝素封装在纳米介孔二氧化硅内部,透明质酸在颗粒外部形成共价连接,包封介孔二氧化硅固定藻蓝胆素,并使之具有特定的靶向性。这一新型靶向纳米颗粒作为光敏剂递送系统能够增强癌细胞对水溶性差的藻蓝胆素的稳定性和摄入,增加生物利用度。
附图说明
图1为本发明实施例1-实施例3的新型靶向纳米颗粒材料对小鼠乳腺癌细胞4T1的暗毒性和光毒性实验结果图;
图2为本发明实施例1的新型靶向纳米颗粒材料的扫描电镜图;
图3为本发明实施例1的新型靶向纳米颗粒材料的傅里叶红外光谱图;
图4为本发明实施例1的新型靶向纳米颗粒材料的激光粒度仪图;
图5为本发明实施例1中的纯藻蓝素的分光光度图;
图6为本发明应用例中新型靶向纳米颗粒材料与癌细胞作用的激光共聚焦显微镜图像。
具体实施方式
下面将通过具体实施例来对本发明进行进一步的解释,然而应当理解,可以以各种形式实现本发明而不应被这里阐述的实施例所限制。相反,提供这些实施例是为了能够更透彻地理解本发明,并且能够将本发明的范围完整的传达给本领域的技术人员。
如无特殊说明,本发明采用各种方法均为常规的方法,各种材料和试剂均能通过商业的途径获得。
实施例1
一种基于藻蓝胆素的新型靶向纳米颗粒的制备方法,所述制备方法为:
1)配制藻蓝素溶液:将从藻蓝蛋白PC中提取的藻蓝素溶解于pH值为6.0-7.4的PBS缓冲液中,得到浓度为10mg/mL的藻蓝素溶液;
其中,从藻蓝蛋白PC中提取藻蓝素PCB的方法,具体为:
①取5-10g PC加入500ml圆底烧瓶中,加入150—300mL甲醇,78—80℃甲醇回流8—16h;
②用纱布初步过滤回流后蓝色液体;
③取过滤后的液体12000r/min离心10min后取深蓝色上清溶液;
④将过滤后的上清经过0.22μm有机相滤膜抽滤2—3遍;
⑤将抽滤后的液体通过旋转蒸发仪,50℃左右浓缩至20—30mL;
⑥将浓缩后的PCB甲醇溶液倒入平板内,加去离子水稀释至甲醇浓度为30%—50%左右;
⑦将平皿用塑料薄膜封紧后放置-80℃冰箱中冷冻;
⑧将冷冻号的平皿放入冷冻干燥机中冷冻干燥1-2天,至制取的PCB粉末成干粉状,即得藻蓝素;如图5所示,取粉末状样品溶解后,经紫外-可见光吸收光谱检验,制备得到的PCB样品特征吸收峰约为684纳米,证明获得了较高纯度的PCB;
所述PBS缓冲液的配方为:氯化钠,8g/L;氯化钾,0.2g/L;磷酸氢二钠,1.44g/L;磷酸二氢钾,0.24g/L;
2)20mg的介孔二氧化硅纳米颗粒(介孔二氧化硅购买厂家为先丰纳米材料科技有限公司)超声分散到40ml的10X PBS缓冲液中,超声混匀2h,得到介孔二氧化硅颗粒溶液;
3)向介孔二氧化硅颗粒溶液中,磁力搅拌下加入藻蓝素溶液10ml;置于室温(25℃)下磁力搅拌24h;藻蓝素可以在静电作用下吸附进入介孔二氧化硅的孔道;
4)取50ml步骤3)所得溶液,12000rpm,30min,4℃,离心一次;
5)将步骤4)所得溶液沉淀,加入含有透明质酸10mg的50ml水中,涡旋2h,再加EDC30mg,涡旋2h;
6)将步骤5)所得溶液,12000rpm,30min,4℃,水洗离心三次,所得沉淀冷冻干燥即得新型靶向纳米颗粒。
本发明实施例1得到的新型靶向纳米颗粒如图2-4所示,其中图2为本发明实施例1的新型靶向纳米颗粒材料的扫描电镜图;图3为本发明实施例1的新型靶向纳米颗粒材料的傅里叶红外光谱图;图4为本发明实施例1的新型靶向纳米颗粒材料的激光粒度仪图。
4℃条件下,纯净水清洗两遍,12000rpm离心30min,三次,弃上清。将水洗后的颗粒进行激光粒度仪(马尔文ZS90,英国)检测结果表明:新型靶向纳米颗粒粒径约为141nm,且颗粒大小均匀。另外将干燥的样品进行扫描电镜和傅里叶红外光谱检测,使用高分辨率场发射扫描电子显微镜(日立S-4800,日本)的检测结果表明:与光滑的空白介孔硅球相对比,新型材料中硅球的表面为透明质酸不均匀覆盖(图2)。进一步的傅里叶红外光谱检测谱图显示,与空白样品对照两者有非常显著的差异(图3),新材料的红外光谱图中出现了波数为3279cm-1(O-H键),1607cm-1((CO)[COO-]键)和1377cm-1((C-H)[CH2](O-H)键)的代表透明质酸的新的红外峰,以上结果以上结果充分表明了新型靶向纳米颗粒材料的成功制备。
实施例2
一种基于藻蓝胆素的新型靶向纳米颗粒的制备方法,所述制备方法为:
1)配制藻蓝素溶液:将提取的藻蓝素溶解于pH值为6.0-7.4的PBS缓冲液中,得到浓度为15mg/mL的藻蓝素溶液;
2)30mg的介孔二氧化硅纳米颗粒超声分散到40ml的10X PBS缓冲液中,超声混匀2h,得到介孔二氧化硅颗粒溶液;
3)向介孔二氧化硅颗粒溶液中,磁力搅拌下加入藻蓝素溶液10ml;置于室温(25℃)下磁力搅拌24h;藻蓝素可以在静电作用下吸附进入介孔二氧化硅的孔道;
4)取50ml步骤3)所得溶液,12000rpm,30min,4℃,离心一次。
5)将步骤4)所得溶液沉淀,加入含有透明质酸10mg的50ml水中,涡旋2h,再加EDC30mg,涡旋2h
6)将步骤5)所得溶液,12000rpm,30min,4℃,水洗离心三次,所得沉淀冷冻干燥即得新型靶向纳米颗粒。
实施例3
一种基于藻蓝胆素的新型靶向纳米颗粒的制备方法,所述制备方法为:
1)配制藻蓝素溶液:将提取的藻蓝素溶解于pH值为6.0-7.4的PBS缓冲液中,得到浓度为20mg/mL的藻蓝素溶液;
2)40mg的介孔二氧化硅纳米颗粒超声分散到40ml的10X PBS缓冲液中,超声混匀2h,得到介孔二氧化硅颗粒溶液;
3)向介孔二氧化硅颗粒溶液中,磁力搅拌下加入藻蓝素溶液10ml;置于室温(25℃)下磁力搅拌24h;藻蓝素可以在静电作用下吸附进入介孔二氧化硅的孔道;
4)取50ml步骤3)所得溶液,12000rpm,30min,4℃,离心一次。
5)将步骤4)所得溶液沉淀,加入含有透明质酸10mg的50ml水中,涡旋2h,再加EDC30mg,涡旋2h;
6)将步骤5)所得溶液,12000rpm,30min,4℃,水洗离心三次,所得沉淀冷冻干燥即得新型靶向纳米颗粒。
应用例
本发明提供一种基于藻蓝胆素的新型靶向纳米颗粒在作为光疗治瘤用光敏剂中的应用。
应用试验如下:
1)癌细胞的培养
小鼠乳腺癌细胞(4T1)于37℃、5%CO2和饱和湿度下,用含10%小牛血清的RMPI-1640培养液培养。收集对数期生长的4T1细胞,无血清培养液离心洗涤三次,去除培养液中的血清。以无血清培养液稀释细胞至106个/mL,接种96孔板,每孔50μL含细胞5×104个。
2)ROS实验
①.RNO的配制:称取5mgRNO溶于2.200ml乙醇,最终混合形成15mM的RNO溶液,然后梯度稀释成所需的15μM的RNO溶液。
②.咪唑的配制:称取5mg咪唑溶于4.896ml水,最终混合形成15mM的咪唑溶液,然后梯度稀释成所需的15μM的咪唑溶液。
③.将透析材料与15μM RNO溶液、15μM咪唑溶液、pH 7.4 10mM的PBS缓冲液1:1:1:1均匀混合于光照小瓶中(可每个加250μL),然后用0.3W/cm2 660nm的激光照射,照射10min,做3个平行实验组。
注:照射时间要按功率大小而定;实验要保证在室温下进行(瓶、试剂都要室温)
④.每种材料做3个平行实验组,以时间为变量,照射10min,每组照射后立即测定OD 440nm的值。在440nm处衰减的RNO可以反映活性氧的变化。活性氧的积累增加会导致RNO吸光值的减少。
注:时间为变量,分别照射0、3、6、9、12、15min;RNO的最大吸收峰在440nm处。
3)体外肿瘤细胞的暗毒性和光毒性实验
进行体外细胞毒性实验。
在每孔50μL含细胞5×104个的小鼠乳腺癌细胞(4T1)的96孔板中加入一系列浓度的新材料样品(采用实施例1所制备的靶向纳米颗粒配置样品,样品以藻蓝胆素含量计分别为0μg/mL,5μg/mL,50μg/mL,100μg/mL,同时用无光照的100μg/mL样品作为对照),加入含有50μg/mL PCB的新介孔材料与肿瘤细胞孵育4h,激光共聚焦显微镜观察下,发射红色荧光的新型靶向纳米颗粒材料吸附在细胞表面显示了其与细胞有很强的相互作用(如图6所示)。
分别进行了下述处理:
处理1:以600-610nm波段的光进行照射,辐射总能量为27J/cm2;
处理2:以550-610nm波段的光进行照射,辐射总能量为80J/cm2;
处理3:以600-630nm波段的光进行照射,辐射总能量为54J/cm2;
可以反映活性氧的变化积累的RNO检测结果表明:随着光照时间的延长,活性氧积累的量呈现明显的时间相关性的积累提高(图5)。24小时后用MTT试剂测定不同给药浓度对细胞的杀伤程度,无光照条件下,高浓度下光敏材料与溶液均对细胞无明显的毒性,细胞基本没有改变,与正常细胞形态一致,说明新型光敏材料本身具有高生物相容性;在相同光照辐射强度下,新型光敏材料对细胞的光毒性随光敏材料的浓度增加而增大,这是因为光敏剂材料的细胞摄取量较多。同样浓度的新型光敏材料和纯藻蓝素对照相比,细胞致死率提高了20%以上,效果非常明显。
在处理1条件下新型光敏材料对小鼠乳腺癌细胞4T1的暗毒性和光毒性实验结果见图1(不同藻蓝素应用浓度下对小鼠乳腺癌细胞4T1的暗毒性和光毒性实验结果图)。此结果进一步证实了肿瘤细胞的死亡,以及新型光敏材料良好的细胞杀伤效果,所以该新型材料可作为光疗治瘤用光敏剂或者药物等。
综上,所述基于藻蓝素和介孔二氧化硅和透明质酸共价组装的新型靶向纳米颗粒材料添加到多种癌细胞培养液中,用680nm波段的光进行照射,测量癌细胞的存活率。结果表明该新型材料不仅稳定性好,而且作为光敏剂治疗癌症效果优良。
介孔二氧化硅纳米颗粒由于其巨大的比表面积,可控孔容和孔隙度,表面含有易于进行多种靶向功能化修饰的丰富Si-OH基团,以及良好的生物相容性、无毒副作用等特性,从而作为一种非常有前途的药物载体广泛应用于设计多功能纳米药物载体系统。
透明质酸可以对许多肿瘤细胞表面过表达的CD44受体具有特异性的识别作用,同时具有卓越的生物相容性、生物可降解性以及对肿瘤细胞的高效识别性,是一种理想的靶向分子。
将新型光敏剂PCB与介孔二氧化硅纳米颗粒和CD44受体靶向的透明质酸相结合,构建出一种新型纳米材料。这种构建的材料能够增大药物负载、保持在血液循环中的稳定性、增加靶向性、减少刺激和降低毒副作用、提高疏水性PCB的细胞膜透过性、增加肿瘤细胞内的特异性积累,从而大大提高药物疗效具有重要的应用价值。
本发明可用其他的不违背本发明的精神或主要特征的具体形式来概述。因此,无论从哪一点来看,本发明的上述实施方案都只能认为是对本发明的说明而不能限制本发明,权利要求书指出了本发明的范围,而上述的说明并未指出本发明的范围,因此,在与本发明的权利要求书相当的含义和范围内的任何改变,都应认为是包括在本发明的权利要求书的范围内。
Claims (6)
1.一种基于藻蓝胆素的新型靶向纳米颗粒的制备方法,其特征在于,步骤包括:
在磁力搅拌下,向介孔二氧化硅颗粒溶液中加入藻蓝素溶液;室温搅拌24h,离心、沉淀后,加入到含有透明质酸的水中,涡旋2h;再加EDC,涡旋2h,水洗离心三次,所得沉淀冷冻干燥即得新型靶向纳米颗粒。
2.如权利要求1所述的制备方法,其特征在于,所述离心条件为:12000rpm,30min,4℃。
3.如权利要求1所述的制备方法,其特征在于,所述藻蓝胆素溶液的配制方法为:将提取的藻蓝素溶解于pH值为6.0-7.4的PBS缓冲液中,得到浓度为5mg/mL的藻蓝素溶液;所述PBS缓冲液的配方为:氯化钠,8g/L;氯化钾,0.2g/L;磷酸氢二钠,1.44g/L;磷酸二氢钾,0.24g/L。
4.如权利要求1所述的制备方法,其特征在于,所述介孔二氧化硅纳米颗粒溶液的配制方法为:介孔二氧化硅纳米颗粒超声分散到40ml的10XPBS缓冲液中,超声混匀2h,得到介孔二氧化硅颗粒溶液。
5.一种基于藻蓝胆素的新型靶向纳米颗粒,其特征在于,如权利要求1-4任一项所述的制备方法制备得到。
6.一种基于藻蓝胆素的新型靶向纳米颗粒的应用,其特征在于,所述新型靶向纳米颗粒在作为光疗治瘤用光敏剂中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110532361.0A CN113230419A (zh) | 2021-05-17 | 2021-05-17 | 一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110532361.0A CN113230419A (zh) | 2021-05-17 | 2021-05-17 | 一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113230419A true CN113230419A (zh) | 2021-08-10 |
Family
ID=77134470
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110532361.0A Pending CN113230419A (zh) | 2021-05-17 | 2021-05-17 | 一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113230419A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115364214A (zh) * | 2022-08-23 | 2022-11-22 | 福州大学 | 一种光动力学疗法的光敏剂及其制备方法和应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103861104A (zh) * | 2014-03-24 | 2014-06-18 | 福州大学 | 一种藻蓝蛋白与酞菁的复合物及其制备方法和应用 |
CN105031669A (zh) * | 2015-06-23 | 2015-11-11 | 上海师范大学 | 一种核壳结构纳米复合材料及其制备方法与应用 |
WO2019040532A1 (en) * | 2017-08-21 | 2019-02-28 | Allele Biotechnology & Pharmaceuticals, Inc. | LIGHT-ABSORBING COMPOSITIONS AND METHODS OF USE |
-
2021
- 2021-05-17 CN CN202110532361.0A patent/CN113230419A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103861104A (zh) * | 2014-03-24 | 2014-06-18 | 福州大学 | 一种藻蓝蛋白与酞菁的复合物及其制备方法和应用 |
CN105031669A (zh) * | 2015-06-23 | 2015-11-11 | 上海师范大学 | 一种核壳结构纳米复合材料及其制备方法与应用 |
WO2019040532A1 (en) * | 2017-08-21 | 2019-02-28 | Allele Biotechnology & Pharmaceuticals, Inc. | LIGHT-ABSORBING COMPOSITIONS AND METHODS OF USE |
Non-Patent Citations (4)
Title |
---|
SANGHYO PARK ET AL.: "Hyaluronic Acid-Conjugated Mesoporous Silica Nanoparticles Loaded with Dual Anticancer Agents for Chemophotodynamic Cancer Therap", 《 JOURNAL OF NANOMATERIALS》 * |
YANG PU ET AL.: "A hybrid biomaterial of biosilica and C-phycocyanin for enhanced photodynamic effect towards tumor cells", 《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》 * |
胡林: "《有序介孔材料与电化学传感器》", 31 December 2013, 合肥工业大学出版社 * |
马丞博: "藻蓝胆素的制备及其作为光敏剂的初步研究", 《中国优秀博硕士学位论文全文数据库(硕士) 工程科技Ⅰ辑 B016-1716》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115364214A (zh) * | 2022-08-23 | 2022-11-22 | 福州大学 | 一种光动力学疗法的光敏剂及其制备方法和应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110201163B (zh) | 一种透明质酸和聚多巴胺修饰的载药介孔二氧化钛纳米粒 | |
Zhang et al. | Near-infrared-triggered in situ hybrid hydrogel system for synergistic cancer therapy | |
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 | |
CN106139144A (zh) | 一种具有协同抗肿瘤特性的透明质酸修饰的金‑碳纳米球及其制备方法与应用 | |
CN107261142B (zh) | 一种用于肿瘤治疗的多孔纳米碳纤维基载药光热试剂及其制备方法 | |
CN106729738A (zh) | 一种枝状金铂双金属纳米粒子及其制备方法和应用 | |
CN107469079B (zh) | 一种t1-mri成像引导下的光动治疗剂制备方法 | |
Tong et al. | A nano-photosensitizer based on covalent organic framework nanosheets with high loading and therapeutic efficacy | |
CN113751079B (zh) | 一种生物材料负载的钙钛矿-二氧化钛纳米复合光催化剂及其构建方法和应用 | |
CN113559064B (zh) | 一种新型自供氧脂质体纳米粒及其制备方法与应用 | |
US20240041787A1 (en) | Photosensitizer molecule and use thereof in increasing tumor retention time and enhancing treatment of large-volume tumors | |
Miao et al. | Recent advances in the biomedical applications of black phosphorus quantum dots | |
CN111714631B (zh) | 近红外驱动的自供氧复合物及其制备方法与应用 | |
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 | |
GB2615705A (en) | Use of artemisinin and derivative thereof in preparation of sensitizer for thermodynamic therapy | |
CN105194679A (zh) | 有抗肿瘤药物纳米层的透明质酸修饰的二氧化钛-氧化石墨烯复合材料制备方法及应用 | |
CN113694023B (zh) | 一种氧化响应型纳米胶束及其制法与应用 | |
Wang et al. | Tumor microenvironment-responsive polymer with chlorin e6 to interface hollow mesoporous silica nanoparticles-loaded oxygen supply factor for boosted photodynamic therapy | |
CN113230419A (zh) | 一种基于藻蓝胆素的新型靶向纳米颗粒及其制备方法 | |
CN111166882B (zh) | 酞菁-rgd多肽-氧化石墨烯复合纳米材料及其制备方法与应用 | |
CN112933229A (zh) | 一种ir820与阿托伐醌无载体自组装纳米粒及其制备方法和应用 | |
CN110251672B (zh) | 一种纳米诊疗剂及其制备方法与应用 | |
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 | |
CN109550050B (zh) | 一种负载黑色素的二氧化钼载药复合物及其制备和应用 | |
Yan et al. | Single-laser excitation synergistic photo-and chemodynamic therapy system based on persistent luminescence nanoparticles |
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 | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210810 |