CN114209828A - 竹红菌素复合纳米粒子及其制备方法 - Google Patents
竹红菌素复合纳米粒子及其制备方法 Download PDFInfo
- Publication number
- CN114209828A CN114209828A CN202111500201.4A CN202111500201A CN114209828A CN 114209828 A CN114209828 A CN 114209828A CN 202111500201 A CN202111500201 A CN 202111500201A CN 114209828 A CN114209828 A CN 114209828A
- Authority
- CN
- China
- Prior art keywords
- hypocrellin
- pluronic
- suspension
- nano
- nanoparticle
- 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
- VANSZAOQCMTTPB-SETSBSEESA-N hypocrellin Chemical compound C1[C@@](C)(O)[C@@H](C(C)=O)C2=C(OC)C(O)=C3C(=O)C=C(OC)C4=C3C2=C2C3=C4C(OC)=CC(=O)C3=C(O)C(OC)=C21 VANSZAOQCMTTPB-SETSBSEESA-N 0.000 title claims abstract description 119
- BQJKVFXDDMQLBE-UHFFFAOYSA-N shiraiachrome A Natural products COC1=C2C3=C(OC)C=C(O)C4=C3C3=C5C(CC(C)(O)C(C(C)=O)C3=C(OC)C4=O)=C(OC)C(=O)C(C(O)=C1)=C25 BQJKVFXDDMQLBE-UHFFFAOYSA-N 0.000 title claims abstract description 116
- KGHNSNSWRMJVND-UHFFFAOYSA-N Hypocrellin Natural products COC1=CC(=O)C2=C3C4C(C(C(=O)C)C(C)(O)Cc5c(OC)c(O)c6C(=O)C=C(OC)C(=C13)c6c45)C(=C2O)OC KGHNSNSWRMJVND-UHFFFAOYSA-N 0.000 title claims abstract description 83
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 63
- 239000002131 composite material Substances 0.000 title claims abstract description 31
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000000725 suspension Substances 0.000 claims abstract description 42
- 210000002377 thylakoid Anatomy 0.000 claims abstract description 32
- 239000012528 membrane Substances 0.000 claims abstract description 25
- 210000004027 cell Anatomy 0.000 claims abstract description 10
- 241001464837 Viridiplantae Species 0.000 claims abstract description 7
- 229920001983 poloxamer Polymers 0.000 claims description 40
- YDLBDQPPRTYAIG-UHFFFAOYSA-N hypocrellin A Natural products COC1C2CC(C)(O)C(C(=O)C)C3=C(OC)C(=O)c4c(O)cc(OC)c5c6c(OC)cc(O)c(C1=O)c6c2c3c45 YDLBDQPPRTYAIG-UHFFFAOYSA-N 0.000 claims description 37
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 33
- 239000000243 solution Substances 0.000 claims description 25
- 239000002244 precipitate Substances 0.000 claims description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 14
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 claims description 14
- 229920001993 poloxamer 188 Polymers 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 229960000502 poloxamer Drugs 0.000 claims description 12
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- APTUSGMALOMQQL-UHFFFAOYSA-N chembl2029624 Chemical compound O=C1C(OC)=C2C(C(C)=O)=C(C)CC3=C(OC)C(=O)C4=C(O)C=C(OC)C5=C4C3=C2C2=C1C(O)=CC(OC)=C25 APTUSGMALOMQQL-UHFFFAOYSA-N 0.000 claims description 10
- 239000000706 filtrate Substances 0.000 claims description 10
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims description 9
- 239000007995 HEPES buffer Substances 0.000 claims description 9
- 238000001132 ultrasonic dispersion Methods 0.000 claims description 9
- 239000008055 phosphate buffer solution Substances 0.000 claims description 8
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 6
- 229940098773 bovine serum albumin Drugs 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 5
- 229930006000 Sucrose Natural products 0.000 claims description 5
- 229960005070 ascorbic acid Drugs 0.000 claims description 5
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 239000005720 sucrose Substances 0.000 claims description 5
- SBMXTMAIKRQSQE-UHFFFAOYSA-N Hypocrellin C Natural products O=C1C=C(OC)C2=C(C3=C45)C(OC)=CC(=O)C3=C(O)C(OC)=C4C(C(C)=O)=C(C)CC3=C5C2=C1C(O)=C3OC SBMXTMAIKRQSQE-UHFFFAOYSA-N 0.000 claims description 4
- 239000007853 buffer solution Substances 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 4
- RYTABHHTUFYVNQ-UHFFFAOYSA-N 3-[4-(2H-tetrazol-5-yl)phenyl]benzoic acid Chemical compound OC(=O)c1cccc(c1)-c1ccc(cc1)-c1nn[nH]n1 RYTABHHTUFYVNQ-UHFFFAOYSA-N 0.000 claims description 3
- LOTVQXNRIAEYCG-UHFFFAOYSA-N 3-hydroxy-2-(hydroxymethyl)-2-[hydroxymethyl(methyl)amino]propanoic acid Chemical compound OCN(C)C(CO)(CO)C(O)=O LOTVQXNRIAEYCG-UHFFFAOYSA-N 0.000 claims description 3
- 229920002025 Pluronic® F 88 Polymers 0.000 claims description 3
- 229920001992 poloxamer 407 Polymers 0.000 claims description 3
- 241000195493 Cryptophyta Species 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 230000009089 cytolysis Effects 0.000 claims description 2
- 238000001125 extrusion Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000000227 grinding Methods 0.000 claims description 2
- 229960002337 magnesium chloride Drugs 0.000 claims description 2
- 229960002668 sodium chloride Drugs 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 11
- 239000001301 oxygen Substances 0.000 abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 8
- 238000005286 illumination Methods 0.000 abstract description 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract description 4
- 230000029553 photosynthesis Effects 0.000 abstract description 3
- 238000010672 photosynthesis Methods 0.000 abstract description 3
- 206010028980 Neoplasm Diseases 0.000 description 8
- -1 amino modified hypocrellin A Chemical class 0.000 description 8
- SEQKRHFRPICQDD-UHFFFAOYSA-N Tricine Natural products OCC(CO)(CO)[NH2+]CC([O-])=O SEQKRHFRPICQDD-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 6
- 239000002088 nanocapsule Substances 0.000 description 6
- 239000003504 photosensitizing agent Substances 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000219315 Spinacia Species 0.000 description 4
- 235000009337 Spinacia oleracea Nutrition 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 239000002211 L-ascorbic acid Substances 0.000 description 3
- 235000000069 L-ascorbic acid Nutrition 0.000 description 3
- UZMAPBJVXOGOFT-UHFFFAOYSA-N Syringetin Natural products COC1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 UZMAPBJVXOGOFT-UHFFFAOYSA-N 0.000 description 3
- 239000007997 Tricine buffer Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- KCFYHBSOLOXZIF-UHFFFAOYSA-N dihydrochrysin Natural products COC1=C(O)C(OC)=CC(C2OC3=CC(O)=CC(O)=C3C(=O)C2)=C1 KCFYHBSOLOXZIF-UHFFFAOYSA-N 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000010586 diagram Methods 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910010272 inorganic material Inorganic materials 0.000 description 2
- 239000011147 inorganic material Substances 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 description 1
- 235000017166 Bambusa arundinacea Nutrition 0.000 description 1
- 235000017491 Bambusa tulda Nutrition 0.000 description 1
- LLWVFANUCOSMDH-UHFFFAOYSA-N C12=CC=C(O)C(C(C=C3)=O)=C2C3=C2C=CC(=O)C3=C2C1=CC=C3O Chemical class C12=CC=C(O)C(C(C=C3)=O)=C2C3=C2C=CC(=O)C3=C2C1=CC=C3O LLWVFANUCOSMDH-UHFFFAOYSA-N 0.000 description 1
- 239000004343 Calcium peroxide Substances 0.000 description 1
- 206010048768 Dermatosis Diseases 0.000 description 1
- 241000143667 Hypocrella Species 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 244000082204 Phyllostachys viridis Species 0.000 description 1
- 235000015334 Phyllostachys viridis Nutrition 0.000 description 1
- 102000004330 Rhodopsin Human genes 0.000 description 1
- 108090000820 Rhodopsin Proteins 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000005975 antitumor immune response Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000011425 bamboo Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- LHJQIRIGXXHNLA-UHFFFAOYSA-N calcium peroxide Chemical compound [Ca+2].[O-][O-] LHJQIRIGXXHNLA-UHFFFAOYSA-N 0.000 description 1
- 235000019402 calcium peroxide Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100001252 long-term toxicity Toxicity 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 208000007578 phototoxic dermatitis Diseases 0.000 description 1
- 231100000018 phototoxicity Toxicity 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 238000009214 sonodynamic therapy Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5063—Compounds of unknown constitution, e.g. material from plants or animals
- A61K9/5068—Cell membranes or bacterial membranes enclosing drugs
-
- 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
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
- A61K41/0033—Sonodynamic cancer therapy with sonochemically active agents or sonosensitizers, having their cytotoxic effects enhanced through application of ultrasounds
-
- 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
- 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
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Nanotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Physics & Mathematics (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- Optics & Photonics (AREA)
- Virology (AREA)
- Botany (AREA)
- Manufacturing & Machinery (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明提供了一种竹红菌素复合纳米粒子及其制备方法,纳米粒子由竹红菌素纳米粒子及其表面包覆的纳米类囊体膜构成,制备方法为将水不溶性的竹红菌素溶解在二甲基亚砜溶液中,然后将该溶液滴加至磷酸盐缓冲液中,超声分散处理,透析,或者,将竹红菌素分散在泊洛沙姆水溶液中,超声分散,得到竹红菌素纳米粒子混悬液;然后在竹红菌素纳米粒子混悬液表面修饰从绿色植物细胞中提取得到的类囊体膜的混悬液,或修饰从微藻细胞中提取得到的类囊体膜的混悬液,再通过微孔滤膜挤压;本发明的复合纳米粒子具有能在光照下进行光合作用产氧的能力,能为竹红菌素的光动力效应或声动力效应提供氧气,从而提高竹红菌素在光照或超声波作用下产出单线态氧的水平。
Description
技术领域
本发明属于材料和生物医学技术领域,具体涉及一种竹红菌素复合纳米粒子及其制备方法,尤其涉及一种在竹红菌素表面包覆纳米类囊体膜,以获得比单纯竹红菌素有更强光动力效应或更强声动力效应的竹红菌素复合纳米粒子的制备方法。
背景技术
竹红菌素,包括包括竹红菌甲素和竹红菌乙素,是从天然竹红菌中提取的3,10-二羟基-4,9-苝醌类衍生物,是一种天然光敏剂,在光照下能高效产生单线态氧,具有光毒性强、暗毒性低、体内代谢快等特点,在肿瘤及皮肤病等疾病光动力治疗中可发挥重要作用。竹红菌素除了在光照下能产生活性氧,在超声波作用下也会产生活性氧,可作为声敏剂用于声动力治疗。然而,竹红菌素是脂溶性药物,难溶于水,生物利用度低,严重影响其药效。即使解决了竹红菌素在水相中的溶解性问题,在乏氧环境仍然不能充分发挥竹红菌素的药效。因为光敏剂产生光动力效应或声敏剂产生声动力效应的一个重要因素,是光敏剂或声敏剂周围要有充足氧气,而肿瘤组织氧分压很低,存在乏氧区域,导致光敏剂或声敏剂难以在肿瘤组织产生大量的单线态氧。
将光敏剂或声敏剂与可以在肿瘤组织产氧的材料如过氧化钙[L.Feng,et al.,Oxygen nanoshuttles for tumor oxygenation and enhanced cancer treatment,CCSChem.1(2019)239–250]、二氧化锰[Guangbao Yang,et al.,Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combinationtherapy favoring antitumor immune responses.Nat.Commun.,2017,8,902]、金属铂[Xue-Liang Liu,et al.Biomimetic Liposomal Nanoplatinum for Targeted CancerChemophototherapy.Advanced Science 2021,51,2003679]等进行复合,可以解决因为肿瘤乏氧而导致光敏剂或声敏剂产生单线态氧效率低不足的问题。然而,这些无机材料在体内降解需要时间,剂量超过一定范围,会产生不可忽视的急毒性和长期毒性,限制了其临床应用。
发明内容
针对现有技术中的不足,本发明的目的是提供竹竹红菌素复合纳米粒子及其制备方法。
为达到上述目的,本发明是将竹红菌素与天然类囊体膜进行复合,通过类囊体的光合作用提供氧气,具体解决方案是:
本发明的第一个方面,提供一种竹红菌素复合纳米粒子,其由竹红菌素纳米粒子及其表面包覆的纳米类囊体膜构成。
进一步地,竹红菌素纳米粒子中竹红菌素选自竹红菌甲素、竹红菌乙素、氨基修饰的竹红菌甲素、氨基修饰的竹红菌乙素、羧基修饰的竹红菌甲素和羧基修饰的竹红菌乙素中的一种以上。其中,竹红菌素的纯度为95-99%,CAS:77029-83-5。
进一步地,纳米类囊体膜是从绿色植物细胞或藻类细胞中提取得到的。
进一步地,纳米类囊体膜的混悬液的制备过程为:将绿色植物与缓冲液混合,研磨,过滤,收集滤液;对滤液进行离心,沉淀再分散在低渗裂解HEPES缓冲液中,然后再离心,收集沉淀,用HEPES缓冲液洗涤沉淀;对沉淀进行超声分散,离心,再分散在水中,之后通过微孔滤膜挤压,得到纳米类囊体膜的混悬液。
其中,缓冲液由三(羟甲基)甲基甘氨酸、蔗糖、抗坏血酸、氯化镁、氯化钠和牛血清白蛋白组成。
本发明的第二个方面,提供一种上述的竹红菌素复合纳米粒子的制备方法,其包括如下步骤:
(1)、竹红菌素纳米粒子混悬液的制备:将竹红菌素溶解在二甲基亚砜溶液中,得到竹红菌素溶液,然后将竹红菌素溶液滴加至磷酸盐缓冲液中,同时进行超声分散处理5-30min,之后透析2-12h,得到竹红菌素纳米粒子混悬液;
或者,将竹红菌素分散在泊洛沙姆水溶液中,超声分散,得到竹红菌素纳米粒子混悬液;
(2)、竹红菌素复合纳米粒子的制备:将步骤(1)的竹红菌素纳米粒子混悬液和上述的纳米类囊体膜的混悬液进行混合,然后经过微孔滤膜挤压,干燥即可。
进一步地,步骤(1)中,泊洛沙姆水溶液中泊洛沙姆选自Pluronic PE系列。
优选地,Pluronic PE系列选自Pluronic L42、Pluronic L43、Pluronic L44、Pluronic L61、Pluronic L62、Pluronic L63、Pluronic L64、Pluronic L65、PluronicL75、Pluronic L85、Pluronic L94、Pluronic F68、Pluronic F88、Pluronic F98、PluronicF108和Pluronic F127中的一种以上。
进一步地,步骤(1)中,竹红菌素和泊洛沙姆的质量比为50:1-1:100。
进一步地,步骤(2)中,微孔滤膜的孔径为800nm、650nm和400nm;挤压的次数为5-20次。
进一步地,步骤(2)中,竹红菌素纳米粒子混悬液和纳米类囊体膜的混悬液的质量比为1:10-10:1。
由于采用上述方案,本发明的有益效果是:
本发明的复合纳米粒子具有能在光照下进行光合作用产氧的能力,能为竹红菌素的光动力效应或声动力效应提供氧气,从而提高竹红菌素在光照或超声波作用下产生单线态氧的水平。
附图说明
图1为本发明的实施例1中竹红菌甲素复合纳米粒子的透射电镜示意图。
图2为本发明的实施例2中Pluronic F68分散的竹红菌甲素水溶液示意图。
图3为本发明的实施例2中Pluronic F68分散的竹红菌甲素表面修饰的纳米类囊体膜的透射电镜示意图(竹红菌甲素与纳米类囊体质量比为1:1)。
图4为本发明的实施例2中Pluronic F68分散的竹红菌甲素表面修饰的纳米类囊体膜的透射电镜示意图(竹红菌甲素与纳米类囊体质量比为1:10)。
图5为本发明的实施例2中Pluronic F68分散的竹红菌甲素表面修饰的纳米类囊体膜的透射电镜示意图(竹红菌甲素与纳米类囊体质量比为10:1)。
具体实施方式
本发明提供了一种竹红菌素复合纳米粒子及其制备方法。
本发明的竹红菌素复合纳米粒子由竹红菌素纳米粒子及其表面包覆的纳米类囊体膜构成。
其中,竹红菌素纳米粒子中竹红菌素选自竹红菌甲素、竹红菌乙素、氨基修饰的竹红菌甲素、氨基修饰的竹红菌乙素、羧基修饰的竹红菌甲素和羧基修饰的竹红菌乙素中的一种以上。
纳米类囊体膜是从绿色植物细胞或藻类细胞中提取得到的。
具体地,纳米类囊体膜的混悬液的制备过程为:将洗净并称量的绿色植物与缓冲液(20mmol/L三(羟甲基)甲基甘氨酸(Tricine)、0.4mol/L蔗糖、2mmol/L抗坏血酸、2mmol/L的MgCl2、40mmol/L的NaCl和0.2%牛血清白蛋白(BSA))混合,在低温(如4℃)条件下研磨,过滤,收集滤液。对滤液进行离心,沉淀再分散在低渗裂解缓冲液(10mmol/L的HEPES,pH值为8.0)中,然后再离心,收集沉淀,用HEPES缓冲液洗涤沉淀。对沉淀再进行超声波分散、离心、再分散在水中,将分散在水中样品通过微孔滤膜挤压,即得纳米类囊体膜的混悬液。
本发明的竹红菌素复合纳米粒子的制备方法包括如下步骤:
(1)、竹红菌素纳米粒子混悬液的制备:将竹红菌素溶解在二甲基亚砜(DMSO)溶液中,得到竹红菌素溶液(即溶有竹红菌素的DMSO溶液),然后将竹红菌素溶液滴加至磷酸盐缓冲液(PBS)中,滴加过程,辅以超声波分散处理5-30min,之后透析2-12h,以除去DMSO,透析外液是PBS,得到竹红菌素纳米粒子混悬液;
或者,将竹红菌素分散在泊洛沙姆(商品名为普兰尼克(Pluronic))水溶液中,超声分散,得到竹红菌素纳米粒子混悬液;
(2)、竹红菌素复合纳米粒子的制备:将步骤(1)的竹红菌素纳米粒子混悬液和纳米类囊体膜的混悬液混合,然后经过孔径为800nm的微孔滤膜挤压5-20次,或者依次以微孔孔径为800nm、650nm、400nm的微孔滤膜进行挤压5-20次,干燥即可。
其中,在步骤(1)中,泊洛沙姆水溶液中泊洛沙姆选自Pluronic PE系列,优选地,Pluronic PE系列选自Pluronic L42、Pluronic L43、Pluronic L44、Pluronic L61、Pluronic L62、Pluronic L63、Pluronic L64、Pluronic L65、Pluronic L75、PluronicL85、Pluronic L94、Pluronic F68、Pluronic F88、Pluronic F98、Pluronic F108和Pluronic F127中的一种以上。
在步骤(1)中,竹红菌素和泊洛沙姆的质量比为50:1-1:100。
在步骤(2)中,竹红菌素纳米粒子混悬液和纳米类囊体膜的混悬液的质量比为1:10-10:1。
以下结合实施例对本发明作进一步的说明。
实施例1:
本实施例的竹红菌甲素复合纳米粒子的制备方法包括如下步骤:
(1)、竹红菌甲素纳米粒子混悬液的制备:称取2mg竹红菌甲素(Hypocrellin A,简称HA),并溶解在1mL的二甲基亚砜(DMSO)溶液中,得到2mg/mL的竹红菌甲素溶液,然后将5μL的竹红菌甲素溶液滴加至1mL的磷酸盐缓冲液(PBS)中,边滴加并用超声波进行分散,滴加结束后,再超声波处理10min,样品透析2h,获得能在PBS中分散的10μg/mL的竹红菌甲素纳米粒子混悬液。
(2)、提取菠菜叶片细胞中的类囊体,制备纳米类囊体膜(Thylakoid membrane,简称TM)的混悬液;制备过程为:配制缓冲液(20mmol/L的Tricine、0.4mol/L蔗糖、2mmol/L抗坏血酸、2mmol/L的MgCl2、40mmol/L的NaCl和0.2%的BSA),将经过4℃预冷的100g新鲜的菠菜叶子与300mL缓冲液混合,研磨,纱布过滤,收集滤液。对滤液进行离心,收集沉淀,将沉淀分散在低渗裂解缓冲液(10mmol/L的HEPES,pH值为8.0)中,2h后,离心,收集沉淀,用10mmol/L的HEPES缓冲液洗涤沉淀2次。将沉淀分散在4℃去离子水中,超声处理10min,再离心,沉淀再分散在去离子水中,再超声处理10min,然后依次通过微孔孔径分别为800nm、400nm、200nm、100nm多孔聚碳酸酯膜挤压,获得纳米类囊体膜的混悬液。
(3)、竹红菌甲素复合纳米粒子(HA/TM)的制备:
将10μg/mL的竹红菌甲素(HA)纳米粒子混悬液和10μg/mL的纳米类囊体膜(TM)的混悬液混合,然后依次通过微孔孔径分别为800nm和400nm的微孔滤膜进行挤压,每个滤膜共挤压5次,即得纳米类囊体膜包覆的竹红菌甲素复合纳米粒子,该竹红菌甲素复合纳米粒子的微观形貌如图1所示。
实施例2:
本实施例的竹红菌甲素复合纳米粒子的制备方法包括如下步骤:
(1)、竹红菌甲素纳米粒子混悬液的制备:配制含0.5mg/mL竹红菌甲素的乙醇溶液共3份,每份0.5mL,置于干燥的小烧杯中,挥干乙醇,得到竹红菌甲素。同时配制含5mg/mL的pluronic F68水溶液,将pluronic F68水溶液加入到上述3个含竹红菌甲素沉淀的小烧杯中,竹红菌甲素与pluronic F68的质量比分别为50:1、1:1、1:100。如图2所示,即使pluronic F68的量较少,pluronic F68也能较好地改善竹红菌甲素在水相中的分散性。
(2)、提取菠菜叶片细胞中的类囊体,制备纳米类囊体膜(Thylakoid membrane,简称TM)的混悬液;制备过程为:配制缓冲液(20mmol/L的Tricine、0.4mol/L蔗糖、2mmol/L抗坏血酸、2mmol/L的MgCl2、40mmol/L的NaCl和0.2%的BSA),将经过4℃预冷的100g新鲜的菠菜叶子与300mL缓冲液混合,研磨,纱布过滤,收集滤液。对滤液进行离心,收集沉淀,将沉淀分散在低渗裂解缓冲液(10mmol/L的HEPES,pH值为8.0)中,2h后,离心,收集沉淀,用10mmol/L的HEPES缓冲液洗涤沉淀2次。将沉淀分散在4℃去离子水中,超声处理10min,再离心,沉淀再分散在去离子水中,再超声处理10min,然后依次通过微孔孔径分别为800nm、400nm、200nm、100nm多孔聚碳酸酯膜挤压,获得纳米类囊体膜的混悬液。
(3)、竹红菌甲素复合纳米粒子的制备:将上述各竹红菌素纳米粒子混悬液和纳米类囊体膜的混悬液混合,分别依次通过微孔孔径分别为800nm和400nm的微孔滤膜进行挤压,挤压方法同上,即得纳米类囊体膜修饰的竹红菌甲素复合纳米粒子,该竹红菌甲素复合纳米粒子的微观形貌分别如图3、图4和图5所示。
其中,质量比为1:1的竹红菌甲素与pluronic F68样品和纳米类囊体膜的混悬液混合,二者浓度和体积如表1所示。
表1
上述对实施例的描述是为了便于该技术领域的普通技术人员能理解和使用本发明。熟悉本领域技术人员显然可以容易的对这些实施例做出各种修改,并把在此说明的一般原理应用到其他实施例中,而不必经过创造性的劳动。因此,本发明不限于上述实施例。本领域技术人员根据本发明的原理,不脱离本发明的范畴所做出的改进和修改都应该在本发明的保护范围之内。
Claims (10)
1.一种竹红菌素复合纳米粒子,其特征在于:其由竹红菌素纳米粒子及其表面包覆的纳米类囊体膜构成。
2.根据权利要求1所述的竹红菌素复合纳米粒子,其特征在于:所述竹红菌素纳米粒子中竹红菌素选自竹红菌甲素、竹红菌乙素、氨基修饰的竹红菌甲素、氨基修饰的竹红菌乙素、羧基修饰的竹红菌甲素和羧基修饰的竹红菌乙素中的一种以上。
3.根据权利要求1所述的竹红菌素复合纳米粒子,其特征在于:所述纳米类囊体膜是从绿色植物细胞或藻类细胞中提取得到的。
4.根据权利要求3所述的竹红菌素复合纳米粒子,其特征在于:所述纳米类囊体膜的混悬液的制备过程为:将绿色植物与缓冲液混合,研磨,过滤,收集滤液;对滤液进行离心,沉淀再分散在低渗裂解HEPES缓冲液中,然后再离心,收集沉淀,用HEPES缓冲液洗涤沉淀;对沉淀进行超声分散,离心,再分散在水中,之后通过微孔滤膜挤压,得到纳米类囊体膜的混悬液。
5.根据权利要求4所述的竹红菌素复合纳米粒子,其特征在于:所述缓冲液由三(羟甲基)甲基甘氨酸、蔗糖、抗坏血酸、氯化镁、氯化钠和牛血清白蛋白组成。
6.一种如权利要求1-5任一项所述的竹红菌素复合纳米粒子的制备方法,其特征在于:其包括如下步骤:
(1)、竹红菌素纳米粒子混悬液的制备:将竹红菌素溶解在二甲基亚砜溶液中,得到竹红菌素溶液,然后将所述竹红菌素溶液滴加至磷酸盐缓冲液中,同时进行超声分散处理5-30min,之后透析2-12h,得到竹红菌素纳米粒子混悬液;
或者,将竹红菌素分散在泊洛沙姆水溶液中,超声分散,得到竹红菌素纳米粒子混悬液;
(2)、竹红菌素复合纳米粒子的制备:将步骤(1)的竹红菌素纳米粒子混悬液与权利要求4的纳米类囊体膜的混悬液进行混合,然后经过微孔滤膜挤压,即可。
7.根据权利要求6所述的制备方法,其特征在于:步骤(1)中,所述泊洛沙姆水溶液中泊洛沙姆选自Pluronic PE系列;
优选地,所述Pluronic PE系列选自Pluronic L42、Pluronic L43、Pluronic L44、Pluronic L61、Pluronic L62、Pluronic L63、Pluronic L64、Pluronic L65、PluronicL75、Pluronic L85、Pluronic L94、Pluronic F68、Pluronic F88、Pluronic F98、PluronicF108和Pluronic F127中的一种以上。
8.根据权利要求6所述的制备方法,其特征在于:步骤(1)中,所述竹红菌素和泊洛沙姆的质量比为50:1-1:100。
9.根据权利要求6所述的制备方法,其特征在于:步骤(2)中,所述微孔滤膜的孔径为800nm、650nm和400nm;所述挤压的次数为5-20次。
10.根据权利要求6所述的制备方法,其特征在于:步骤(2)中,所述竹红菌素纳米粒子混悬液和纳米类囊体膜的混悬液的质量比为1:10-10:1。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111500201.4A CN114209828A (zh) | 2021-12-09 | 2021-12-09 | 竹红菌素复合纳米粒子及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111500201.4A CN114209828A (zh) | 2021-12-09 | 2021-12-09 | 竹红菌素复合纳米粒子及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN114209828A true CN114209828A (zh) | 2022-03-22 |
Family
ID=80700535
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111500201.4A Pending CN114209828A (zh) | 2021-12-09 | 2021-12-09 | 竹红菌素复合纳米粒子及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114209828A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115491342A (zh) * | 2022-08-22 | 2022-12-20 | 浙江大学 | 用于红光激发下产生atp和nadph的纳米材料及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1565433A (zh) * | 2003-07-03 | 2005-01-19 | 中国科学院化学研究所 | 竹红菌素水溶性纳米粒及用途 |
US20100262115A1 (en) * | 2009-04-07 | 2010-10-14 | Intelligentnano Inc. | Nanoparticles for cancer sonodynamic and photodynamic therapy |
CN108245676A (zh) * | 2016-12-27 | 2018-07-06 | 中国科学院理化技术研究所 | 一种竹红菌素衍生物纳米组装体及其应用 |
-
2021
- 2021-12-09 CN CN202111500201.4A patent/CN114209828A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1565433A (zh) * | 2003-07-03 | 2005-01-19 | 中国科学院化学研究所 | 竹红菌素水溶性纳米粒及用途 |
US20100262115A1 (en) * | 2009-04-07 | 2010-10-14 | Intelligentnano Inc. | Nanoparticles for cancer sonodynamic and photodynamic therapy |
CN108245676A (zh) * | 2016-12-27 | 2018-07-06 | 中国科学院理化技术研究所 | 一种竹红菌素衍生物纳米组装体及其应用 |
Non-Patent Citations (1)
Title |
---|
YAN CHENG ET AL: "Thylakoid Membranes with Unique Photosystems Used to Simultaneously Produce Self-Supplying Oxygen and Singlet Oxygen for Hypoxic Tumor Therapy", 《ADVANCED HEALTHCARE MATERIALS》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115491342A (zh) * | 2022-08-22 | 2022-12-20 | 浙江大学 | 用于红光激发下产生atp和nadph的纳米材料及其制备方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Guan et al. | BODIPY-decorated nanoscale covalent organic frameworks for photodynamic therapy | |
Ding et al. | A multimodal Metal-Organic framework based on unsaturated metal site for enhancing antitumor cytotoxicity through Chemo-Photodynamic therapy | |
CN104800846B (zh) | 一种核壳型金纳米材料及其制备方法和应用 | |
CA2513759C (en) | Ceramic based nanoparticles for entrapping therapeutic agents for photodynamic therapy and method of using same | |
Jia et al. | Self‐assembled carbon dot nanosphere: a robust, near‐infrared light‐responsive, and vein injectable photosensitizer | |
Wang et al. | Reconstructing the intracellular pH microenvironment for enhancing photodynamic therapy | |
CN104491871B (zh) | 一种基于聚谷氨酸和胱胺的pH与还原敏感性的纳米微凝胶 | |
CN112999153B (zh) | 载化疗药物/光敏剂的纳米胶束及其制备方法和应用 | |
Song et al. | Fabrication of the biomimetic DOX/Au@ Pt nanoparticles hybrid nanostructures for the combinational chemo/photothermal cancer therapy | |
Du et al. | NIR-activated multi-hit therapeutic Ag2S quantum dot-based hydrogel for healing of bacteria-infected wounds | |
CN111558051B (zh) | 一种具有快速粘液渗透作用的复合纳米微球及其制备方法和应用 | |
Qiu et al. | Hollow mesoporous carbon nanospheres for imaging-guided light-activated synergistic thermo-chemotherapy | |
CN111773245A (zh) | 一种复合纳米酶及其制备方法与应用 | |
Sun et al. | A Pd corolla–human serum albumin–indocyanine green nanocomposite for photothermal/photodynamic combination therapy of cancer | |
CN114209828A (zh) | 竹红菌素复合纳米粒子及其制备方法 | |
CN113975234A (zh) | 一种羟基-α-山椒素纳米脂质体及其制备方法 | |
Wang et al. | Defect-engineered porphyrinic metal–organic framework nanoparticles for targeted multimodal cancer phototheranostics | |
Yin et al. | Recent development of MOF-based photothermal agent for tumor ablation | |
Zhou et al. | Chem-inspired hollow ceria nanozymes with lysosome-targeting for tumor synergistic phototherapy | |
Liang et al. | A monomeric photosensitizer for targeted cancer therapy | |
Su et al. | Photothermal-driven disassembly of naphthalocyanine nano-photosensitizers for photothermal and photodynamic therapy | |
Cui et al. | Biomimetic light-activatable graphene-based nanoarchitecture for synergistic chemophotothermal therapy | |
Wang et al. | Rod-like BODIPY nanomaterials with enhanced photodynamic activity | |
Shu et al. | Photodynamic and photothermal therapy-driven synergistic cancer treatment assisted by zeolitic imidazolate framework-8: A review | |
Chen et al. | In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing |
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 |
Application publication date: 20220322 |
|
RJ01 | Rejection of invention patent application after publication |