CN113713096B - 一种萘酞菁铜与Au复合材料及其制备方法和应用 - Google Patents
一种萘酞菁铜与Au复合材料及其制备方法和应用 Download PDFInfo
- Publication number
- CN113713096B CN113713096B CN202111041857.4A CN202111041857A CN113713096B CN 113713096 B CN113713096 B CN 113713096B CN 202111041857 A CN202111041857 A CN 202111041857A CN 113713096 B CN113713096 B CN 113713096B
- Authority
- CN
- China
- Prior art keywords
- naphthalocyanine
- copper
- chloroform
- composite material
- solution
- 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.)
- Active
Links
- LKKPNUDVOYAOBB-UHFFFAOYSA-N naphthalocyanine Chemical compound N1C(N=C2C3=CC4=CC=CC=C4C=C3C(N=C3C4=CC5=CC=CC=C5C=C4C(=N4)N3)=N2)=C(C=C2C(C=CC=C2)=C2)C2=C1N=C1C2=CC3=CC=CC=C3C=C2C4=N1 LKKPNUDVOYAOBB-UHFFFAOYSA-N 0.000 title claims abstract description 72
- 229910052802 copper Inorganic materials 0.000 title claims abstract description 68
- 239000010949 copper Substances 0.000 title claims abstract description 68
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 239000002131 composite material Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 62
- 239000010931 gold Substances 0.000 claims abstract description 50
- 239000000243 solution Substances 0.000 claims abstract description 34
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052737 gold Inorganic materials 0.000 claims abstract description 22
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 21
- 239000002105 nanoparticle Substances 0.000 claims abstract description 18
- 239000007864 aqueous solution Substances 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000009210 therapy by ultrasound Methods 0.000 claims abstract description 7
- 239000002244 precipitate Substances 0.000 claims abstract description 5
- 239000000523 sample Substances 0.000 claims abstract description 5
- 238000002156 mixing Methods 0.000 claims abstract description 4
- 238000000926 separation method Methods 0.000 claims abstract description 3
- 239000011259 mixed solution Substances 0.000 claims description 11
- 238000003756 stirring Methods 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 239000005457 ice water Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 2
- 239000012216 imaging agent Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 23
- 238000001338 self-assembly Methods 0.000 abstract description 15
- 239000002245 particle Substances 0.000 abstract description 11
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 5
- 238000007626 photothermal therapy Methods 0.000 abstract description 4
- 239000000203 mixture Substances 0.000 abstract description 3
- 206010021143 Hypoxia Diseases 0.000 abstract description 2
- 230000007954 hypoxia Effects 0.000 abstract description 2
- 238000002428 photodynamic therapy Methods 0.000 abstract description 2
- 230000035945 sensitivity Effects 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 19
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 14
- 239000002609 medium Substances 0.000 description 12
- 239000002114 nanocomposite Substances 0.000 description 11
- 239000002086 nanomaterial Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 239000006185 dispersion Substances 0.000 description 8
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 7
- 238000003384 imaging method Methods 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- QGLWBTPVKHMVHM-KTKRTIGZSA-N (z)-octadec-9-en-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCN QGLWBTPVKHMVHM-KTKRTIGZSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000000862 absorption spectrum Methods 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000009214 sonodynamic therapy Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 229940123973 Oxygen scavenger Drugs 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000022534 cell killing Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- JJIWQZDKAOMTKU-UHFFFAOYSA-N copper 5,12,18,25,31,38,44,51-octabutoxy-2,15,28,41,53,55-hexaza-54,56-diazanidatridecacyclo[40.10.1.13,14.116,27.129,40.04,13.06,11.017,26.019,24.030,39.032,37.043,52.045,50]hexapentaconta-1,3,5,7,9,11,13,15,17,19,21,23,25,27(55),28,30,32,34,36,38,40,42(53),43,45,47,49,51-heptacosaene Chemical compound [Cu+2].C=12C(OCCCC)=C3C=CC=C[C]3C(OCCCC)=C2C(N=C2[N-]C(C3=C(OCCCC)C4=CC=CC=C4C(OCCCC)=C32)=NC2=NC(C3=C(OCCCC)C4=CC=CC=C4C(OCCCC)=C32)=N2)=NC=1N=C1[C]3C(OCCCC)=C4C=CC=CC4=C(OCCCC)C3=C2[N-]1 JJIWQZDKAOMTKU-UHFFFAOYSA-N 0.000 description 2
- HYTWSZKAHPYXCU-UHFFFAOYSA-L disodium;3-[10-(2-carboxylatoethyl)anthracen-9-yl]propanoate Chemical group [Na+].[Na+].C1=CC=C2C(CCC(=O)[O-])=C(C=CC=C3)C3=C(CCC([O-])=O)C2=C1 HYTWSZKAHPYXCU-UHFFFAOYSA-L 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- RBTKNAXYKSUFRK-UHFFFAOYSA-N heliogen blue Chemical compound [Cu].[N-]1C2=C(C=CC=C3)C3=C1N=C([N-]1)C3=CC=CC=C3C1=NC([N-]1)=C(C=CC=C3)C3=C1N=C([N-]1)C3=CC=CC=C3C1=N2 RBTKNAXYKSUFRK-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- QQEVAEVDNGPTQA-UHFFFAOYSA-N n-boranyl-2-methylpropan-2-amine Chemical compound BNC(C)(C)C QQEVAEVDNGPTQA-UHFFFAOYSA-N 0.000 description 2
- 239000002073 nanorod Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000007669 thermal treatment Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 210000003771 C cell Anatomy 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 238000001720 action spectrum Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- DUEPRVBVGDRKAG-UHFFFAOYSA-N carbofuran Chemical compound CNC(=O)OC1=CC=CC2=C1OC(C)(C)C2 DUEPRVBVGDRKAG-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000001553 co-assembly Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 150000004699 copper complex Chemical class 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001827 electrotherapy Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000004687 hexahydrates Chemical class 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000006911 nucleation Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 238000013021 overheating Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000001931 thermography Methods 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 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
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
-
- 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
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
-
- 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)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Manufacturing & Machinery (AREA)
- Radiology & Medical Imaging (AREA)
- Acoustics & Sound (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
本申请公开一种萘酞菁铜自组装材料、萘酞菁铜与Au复合材料及其制备方法和应用,包括以下步骤:(1)配制萘酞菁铜的氯仿溶液;(2)配制Au的氯仿(3)配制不同浓度的SDS水溶液;(4)将步骤(1)的溶液加入到步骤(3)中或将步骤(1)和步骤(2)的溶液混合后加入到步骤(3)中,探针超声后水浴挥发,离心分离,所得沉淀即为萘酞菁铜自组装材料及其与金纳米颗粒复合材料。该方法由于金颗粒的引入,有效的响应肿瘤微环境中过表达的H2O2,一方面解决肿瘤乏氧问题的同时,有效增强了萘酞菁铜的声动力治疗性能。该方法简单、高效,可大量制备,最终用于光热治疗和声动力治疗试剂中,具有光热性能好、用量少、增强声敏明显等优点。
Description
技术领域
本发明属于材料化学、有机超分子化学与生物纳米医药领域,具体涉及一种萘酞菁铜自组装材料、萘酞菁铜与Au复合材料及其制备方法和应用。
背景技术
随着社会的发展与环境的持续恶化、人口老龄化等问题的加剧,癌症发病率和死亡率正迅速增长。寻找适当高效的癌症治疗方法,延长患者生命迫切重要。目前癌症的临床治疗手段主要有手术、化疗和放疗等。然而,这些治疗技术都存在一定的局限性。如何实现更加高效精准的治疗,已成为癌症治疗过程中亟待解决的难题。光热治疗通过局部过热产生较好的治疗效果,具有疗法简单、高效、选择性好、适用性强、无创等优势,但受光穿透深度限制,进而导致癌细胞的不完全消除和肿瘤的复发,实现肿瘤的完全消除仍需要与其他治疗方式联合。声动力疗法将声能聚焦于深部组织,激活声敏剂产生活性氧,抑制肿瘤。由于超声具有穿透性,对深部肿瘤的治疗无需借助其它手段,声动力治疗设备简单,造价低,与手术、放疗、化疗等传统治疗肿瘤的方式相比,声动力治疗具有微创性、实时性、安全性等优势。因此开发高效的声敏剂是该领域研究的关键。传统的无机声敏剂产生的电子空穴对极易复合、治疗效率较低,需与其他材料复合实现较好的治疗效果。常用的有机声敏剂组成比例不稳定,排泄缓慢,其作用光谱不理想,且这类敏感物质并非特异性很强的物质等因素,严重影响了声动力学疗法的实际效果及其临床实际应用。开发组成结构明确、特异性强的声敏剂将是声动力疗法领域中的重要研究方向。而如何构筑具有较高光热转换效率的光热试剂,同时赋予其较强的声动力治疗效果进而实现联合治疗,仍是研究的难点。
金属酞菁是一类特殊的大π共轭体系化合物,具有多种多样的取代基,几乎可以和元素周期表中所有的金属元素发生配位,较大的环状结构,较强的刚性,良好的热稳定性和化学稳定性、电子缓冲性、光电磁性等优点,广泛应用在光电转换、小分子催化活化、信息储存、生物模拟及工业染料等领域。萘酞菁特有的大环平面共辄体系使分子的基态能量很低,因而萘酞菁具有很好的物理和化学稳定性,耐光、耐热、耐酸碱、耐水浸等优点,然而无取代萘酞菁几乎不溶于有机溶剂,极大的限制其应用。如何改进其亲水性,并赋予其优异的生物治疗性能仍是其研究的难点。
发明内容
本发明的目的在于提供一种萘酞菁铜自组装材料、萘酞菁铜与Au复合材料及其制备方法和应用。
基于上述目的,本发明采取如下技术方案:
一种萘酞菁铜自组装材料、萘酞菁铜与Au复合材料的制备方法,包括以下步骤:
1)将萘酞菁铜溶于氯仿中,得到萘酞菁铜的氯仿溶液;
2)将金纳米颗粒分散在氯仿中,得到Au的氯仿溶液;
3)配制0.0025 mol/L~0.015 mol/L 的SDS水溶液;
4)室温下,将步骤1)得到的溶液加入到步骤3)中;或者将步骤1)得到的溶液加入到步骤2)中,超声混合3~6 min,得到萘酞菁铜/金纳米颗粒/氯仿混合溶液,将萘酞菁铜/金纳米颗粒/氯仿混合溶液加入到步骤3)中;
5)在室温搅拌下,将步骤4)得到的溶液探针超声1~3min,超声后将混合溶液转移至62~70℃水浴锅中,搅拌挥发出部分溶剂,冰水浴冷却至室温,离心分离,所得沉淀即为萘酞菁铜自组装材料或萘酞菁铜与Au复合材料。
优选地,所述的萘酞菁铜为5,9,14,18,23,27,32,36-八丁氧基-2,3-萘酞菁铜(II),其氯仿溶液浓度为10~20 mg/mL;Au的氯仿溶液的浓度为30~50mg/mL。
优选地,步骤4)中萘酞菁铜与金纳米颗粒的质量比为1:(3~5),步骤4)中,步骤1)的溶液与SDS水溶液体积比为1:5~15,萘酞菁铜/金纳米颗粒/氯仿混合溶液与SDS水溶液体积比为1:5~15。
上述制备方法制得的萘酞菁铜自组装材料以及萘酞菁铜与Au复合材料。
上述制备方法制得的萘酞菁铜自组装材料在制备光热治疗肿瘤药物中的应用,以及萘酞菁铜与Au复合材料在制备声动力治疗肿瘤药物中的应用。
优选地,上述肿瘤是指宫颈癌。
上述制备方法制得的萘酞菁铜与Au复合材料作为生物组织中的光声成像剂、示踪剂的应用。
Au纳米颗粒具体制备方法如下:分别取10mL油胺和10mL正辛烷注入50mL两口圆底烧瓶中,然后置于20℃恒温水浴中搅拌5~10min。在通入N2保护下,往混合液中加入0.1g氯金酸,继续搅拌5~10min,然后加入2mL的叔丁基氨硼烷的正辛烷和油胺混合溶液(0.25g叔丁基氨硼烷粉末溶解于1mL正辛烷和1mL油胺中),继续搅拌1h后停止。取出,加入60mL无水乙醇沉降,6000r/min离心5min,沉淀用乙醇洗三次后,将沉淀分散于10mL氯仿中备用,即得到尺寸为6nm左右的Au颗粒/氯仿分散液。参考文献:(郑南峰,刘圣杰,方晓亮,吴炳辉,田中群。一种油溶性金纳米颗粒的合成方法。CN, CN103769605 A[P].)。
在本发明中,结合光热治疗和声动力治疗体系的特点,以具有大π共轭结构的萘酞菁为组装基元,同时以具有肿瘤微环境响应可以催化过表达的H2O2产生氧气的小尺寸金纳米颗粒作为共自组装基元,在合成过程中在Au颗粒表面引入大量的烷基链,增加其油相分散性,进而与萘酞菁铜上的取代基产生疏水-疏水作用,在倒入乳化剂的水溶液及后续的有机溶剂挥发的过程中,二者共同析出成核,再沉淀共组装构筑纳米试剂。在本发明中,通过调控乳化剂的浓度,萘酞菁铜的浓度,一方面制备得到尺寸均一、形貌规整、产率高、可大规模制备的萘酞菁铜自组装以及与金复合纳米短棒;另一方面乳化剂的加入极大增加了萘酞菁铜的亲水性,有利于提高其生物相容性,进而提高组装体的吞噬量。在本发明中,组装后分子间成强烈的π堆积,抑制了荧光发射,增强非辐射跃迁,产生的大量的热量,从而提高了光热治疗效率以及近红外光热成像功能;另一方面,聚集之后,铜的配合物光敏特性降低,进而展现出声敏特性,在超声辐射下,可以产生大量的ROS,同时金颗粒催化肿瘤微环境中过表达的H2O2,从而为SDT提供氧气,进而显著增加萘酞菁铜超声辐射产生ROS的能力。该试剂在近红外区具有较高的光谱吸收、较高的光热转换效率,同时,该试剂表现出优良的组织穿透深度的光声成像效果,进而具有优良的光声成像、声动力治疗与光热治疗多功能于一体的联合功能,这可能为探索智能、准确和无创高效的联合治疗开辟一条新途径。
在本发明中,由于金颗粒的引入,一方面它在近红外区具有较高的光谱吸收、较高的光热转换效率,有效解决肿瘤治疗中的乏氧问题,提高超声辐射产生ROS的能力,增强声动力治疗效果,进而实现高效联合治疗杀死癌细胞;另一方面,萘酞菁铜纳米化增强其亲水性,有利于提高其生物相容性,进而提高吞噬量,提高其在病灶位置的有效浓度。同时,复合材料优异的光声成像(PA)可以实时监测深层肿瘤组织处纳米药物积累情况,为实时监测治疗提供依据。
附图说明
图1为实施例1产物,不同SDS浓度下所合成的萘酞菁铜纳米材料的SEM图(图1A-D分别对应SDS的浓度为0.0025 mol/L、0.01 mol/L、0.0125 mol/L、0.015 mol/L);
图2为实施例2产物,在SDS浓度为0.015 mol/L时萘酞菁铜与金纳米颗粒复合材料的TEM图;
图3为实施例1产物萘酞菁铜的单体及其自组装体的紫外吸收光谱图;
图4为实施例1产物的光热性能测试图;
图5为实施例2产物的声敏超声产生单线态氧性能测试图;
图6为实施例1产物的光声成像测试图;
图7为实施例1产物的体外光热测试图;
图8为实施例2产物的体外声动力测试图。
具体实施方式
以下结合具体实施例对本发明的技术方案作进一步详细说明,但本发明的保护范围并不局限于此。
下述实施例中的SDS化学名为十二烷基硫酸钠,购自Sigma-Aldrich,CAS号:151-21-3;5,9,14,18,23,27,32,36-八丁氧基-2,3-萘酞菁铜(II),购自百灵威科技,CAS号:155773-67-4;六水合氯金酸,购自北京华威锐科化工有限公司,CAS号:16903-35-8;ADPA化学名为蒽-9,10-二丙酸二钠盐(CAS号: 82767-90-6),购自阿拉丁。
实施例1
一种萘酞菁铜自组装纳米材料的制备方法,包括以下步骤:
1)称取10 mg萘酞菁铜溶于1 mL氯仿中,配制成10 mg/mL的溶液;
2)配制10 mL浓度为0.0025 mol/L的SDS水溶液;
3)搅拌下,将步骤1)中的1 mL溶液全部快速注入到步骤2)的溶液中,探针超声2min(功率为80 W),然后转入65℃水浴中,搅拌下快速挥发10 min,挥发掉全部的氯仿溶液,然后冰水浴中快速冷却至室温,13000r/min离心,所得沉淀即为萘酞菁铜自组装纳米材料,SEM图片详见图1A。
与上述方案不同之处在于:更换步骤2)中SDS的浓度分别为0.01 mol/L (图1B)、0.0125 mol/L (图1C)、0.015 mol/L (图1D) 时得到萘酞菁铜自组装材料。
SEM图如图1所示,不同乳化剂水溶液浓度时均得到纳米短棒,SEM的粒径统计结果表明图1中A-D所示,短棒长和宽依次分别约为121nm和54nm,118nm和50nm,113nm和51nm,88nm和39nm。纳米短棒分散均匀,形貌规整,尺寸均一。为了研究萘酞菁铜组装体的组装方式,本申请进行了紫外可见吸收光谱测试,如图3所示,组装体与铜酞菁单分子相比,吸收光谱发生了明显的拓宽和红移,最大吸收光谱由单体的850 nm红移至860 nm,且在769 nm处的吸收明显增强。
实施例2
一种萘酞菁铜与Au复合材料的制备方法,包括以下步骤:
1)将10 mg萘酞菁铜溶于0.5mL氯仿中,配制得到20 mg/mL萘酞菁铜/氯仿溶液;
2)将合成的金纳米颗粒分散在氯仿中,配制得到40 mg/mL的Au/氯仿溶液;
3)室温下,将步骤1)得到的0.5 mL溶液加入到步骤2)的0.5 mL溶液中,超声混合3~6 min,配制得到萘酞菁铜/金纳米颗粒/氯仿混合溶液;
4)配制10 mL浓度为0.015 M的SDS水溶液;
5)将步骤3)的溶液加入到步骤4)的溶液中,探针超声2 min(功率为80 W),65℃水浴挥发10 min,挥发掉全部的氯仿溶液,然后冰水浴中快速冷却至室温,13000r/min离心,所得沉淀即为萘酞菁铜与金颗粒共组装复合纳米材料。
TEM图片如图2所示,金颗粒主要分布在萘酞菁铜纳米棒的两端。
对实施例1中SDS浓度为0.015 mol/L时得到的萘酞菁铜纳米棒不同浓度(2、5、10、20、40 μg/mL)的水分散液(水分散液的制备是将材料加入去离子水中超声分散即可,下同),采用808nm激光器1.5 W/cm2进行激光照射10 min,并监测温度变化,如图4所示。溶液的温度随着浓度的增加而增加,表现出浓度依赖的温度变化。从图中可以发现,随铜酞菁组装体浓度的增加,升温速度增快,在纳米短棒浓度为40 μg/mL,10min纳米材料温度可以升至82℃,说明了纳米材料具有良好的光热性能。
对实施例2中的浓度为1 mg/mL的复合材料水分散液,取20 μL分散在3mL溶有活性氧捕获剂ADPA的水溶液中,ADPA浓度为0.1 mg/mL。采用(Chattanooga IntelectTransport Electrotherapy/Ultrasound Combo Unit,美国,厂家Advantage Medical -Physical Therapy Equipment Supplier, a division of Scrip, Inc.)声动力治疗仪进行超声辐射,功率为1 W/cm2,频率为1 Hz,时间10 min,如图5所示,随着超声(US)时间的增加,活性氧捕获剂ADPA在350-400 nm间吸收值逐渐降低,表明超声刺激纳米材料有利于ROS的产生。
对实施例1中SDS浓度为0.015 mol/L制得的萘酞菁铜自组装材料,将其配制成不同浓度(25、50、100、200、400 μg/mL)的纳米材料水分散液,采用多模式小动物超声/光声成像系统(美国,厂家Fujifilm Visual Sonics, 型号VEVO LAZR-X,激光波长680nm~970nm)测试其光声成像信号,如图6所示。随着浓度的增加信号强度逐渐增加,表现出良好的浓度-信号的线性关系。信号强度-光谱的曲线图中看出,光声信号强度在880nm处达到最大。
对实施例2中的复合材料进行光热杀死肿瘤细胞实验。将添加有10%的胎牛血清(FBS)、1%的青霉素-链霉素以及1%的非必须氨基酸的高糖培养基(以下实验所用到的培养基均是此培养基,具体为:50mL的胎牛血清(FBS)、5mL的青霉素-链霉素以及5mL的非必须氨基酸加入到500mL的DMEM中混合均匀即可)的HeLa细胞按照5×103个/孔接种到96孔板中,然后放置在5%的CO2浓度、37°C的细胞培养箱中培养12小时。对实施例2的纳米复合材料进行不同浓度(0 μM、50 μM、100 μM、200 μM)的配制:首先配制1 mg/mL的纳米复合材料培养基分散液(将材料均匀分散到上述的培养基中),分别取50 μL、100 μL、200 μL稀释到1 mL培养基中得到浓度50 μM、100 μM、200 μM的纳米复合材料,0 μM为不含纳米复合材料的培养基。取100 μL所配制的各种浓度的纳米复合材料培养基分散液与孔中HeLa细胞共孵育6小时,随后,去除培养基,将细胞用PBS缓慢清洗两次,采用808 nm波长的激光(0.7 W/cm2)连续照射各种时间段3分钟、6分钟、9分钟,并与未光照组对比。随后,将细胞继续孵育12小时,孵化结束除去培养基,然后向每个孔中添加100 μL的CCK-8溶液(使用培养基稀释至1/10浓度),再孵育60分钟后取出。采用多功能酶标仪在450 nm处测量光吸收值,并计算活细胞的生存率,确定材料对细胞的暗毒性及光热杀伤效果。所得结果如图7所示,光照3 min时,纳米复合材料浓度为0 μM、50 μM、100 μM、200 μM细胞存活率依次约为100%、94%、90%、64%;光照6 min时,纳米复合材料浓度为0 μM、50 μM、100 μM、200 μM细胞存活率依次约为100%、87%、80%、43%;光照9 min时,纳米复合材料浓度约为0 μM、50 μM、100 μM、200 μM细胞存活率依次约为100%、84%、56%、29%。随着浓度的增加和光照时间的延长,细胞存活率逐渐下降,表现出明显的浓度和光照时间依赖的细胞杀伤效果。
与肿瘤细胞的光热(PTT)实验不同之处在于,声动力治疗实验(US)中将实施例2中的纳米材料的培养基分散液(0 μM、50 μM、100 μM、200 μM)与HeLa细胞共培养,然后实验组使用声动力治疗仪,超声功率为1 W/cm2,频率为1 Hz,连续辐射不同时间段3 min和5 min。随后采用上述的MTT实验计算活细胞的生存率,最终确定材料对细胞的暗毒性以及超声杀伤肿瘤细胞的效果,如图8所示,连续辐射3 min时,纳米复合材料浓度为0 μM、50 μM、100 μM、200 μM细胞存活率依次约为100%、93%、88%、83%;连续辐射5 min时,纳米复合材料浓度为0 μM、50 μM、100 μM、200 μM细胞存活率依次约为93%、87%、79%、65%。
Claims (6)
1.一种萘酞菁铜与Au复合材料的制备方法,其特征在于,包括以下步骤:
1)将萘酞菁铜溶于氯仿中,得到萘酞菁铜的氯仿溶液;所述的萘酞菁铜为5,9,14,18,23,27,32,36-八丁氧基-2,3-萘酞菁铜;
2)将金纳米颗粒分散在氯仿中,得到Au的氯仿溶液;
3)配制0.0025 mol/L~0.015 mol/L 的SDS水溶液;
4)室温下,将步骤1)得到的溶液加入到步骤2)中,超声混合3~6 min,得到萘酞菁铜/金纳米颗粒/氯仿混合溶液,将萘酞菁铜/金纳米颗粒/氯仿混合溶液加入到步骤3)中;
5)在室温搅拌下,将步骤4)得到的溶液探针超声1~3min,超声后将混合溶液转移至62~70℃水浴锅中,搅拌挥发出氯仿,冰水浴冷却至室温,离心分离,所得沉淀即为萘酞菁铜与Au复合材料。
2.根据权利要求1所述萘酞菁铜与Au复合材料的制备方法,其特征在于,萘酞菁铜的氯仿溶液浓度为10~20 mg/mL;Au的氯仿溶液的浓度为30~50mg/mL。
3.根据权利要求1所述的萘酞菁铜与Au复合材料的制备方法,其特征在于,步骤4)中萘酞菁铜与金纳米颗粒的质量比为1:3~5,步骤4)中,萘酞菁铜/金纳米颗粒/氯仿混合溶液与SDS水溶液体积比为1:5~15。
4.权利要求1至3任一所述的制备方法制得的萘酞菁铜与Au复合材料。
5.权利要求4所述的萘酞菁铜与Au复合材料在制备声动力治疗肿瘤药物中的应用。
6.权利要求4所述的萘酞菁铜与Au复合材料在制备作为生物组织中的光声成像剂、示踪剂的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111041857.4A CN113713096B (zh) | 2021-09-07 | 2021-09-07 | 一种萘酞菁铜与Au复合材料及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111041857.4A CN113713096B (zh) | 2021-09-07 | 2021-09-07 | 一种萘酞菁铜与Au复合材料及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113713096A CN113713096A (zh) | 2021-11-30 |
CN113713096B true CN113713096B (zh) | 2022-06-24 |
Family
ID=78682093
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111041857.4A Active CN113713096B (zh) | 2021-09-07 | 2021-09-07 | 一种萘酞菁铜与Au复合材料及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113713096B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130315837A1 (en) * | 2012-02-23 | 2013-11-28 | Canon Kabushiki Kaisha | Dye-containing nanoparticle for photoacoustic contrast agent |
US20150037255A1 (en) * | 2013-07-30 | 2015-02-05 | Canon Kabushiki Kaisha | Phthalocyanine dye-containing contrast agent for photoacoustic imaging |
CN108940365A (zh) * | 2018-06-25 | 2018-12-07 | 山东大学 | 一种制备酞菁铁水溶性分散纳米粒子的方法 |
CN109260473A (zh) * | 2018-10-18 | 2019-01-25 | 河南大学 | 一种具有肿瘤靶向功能的卟啉纳米复合物及其制备方法和应用 |
WO2020205729A1 (en) * | 2019-03-29 | 2020-10-08 | The Brigham And Women's Hospital, Inc. | Targeted synergistic cancer immunotherapy |
-
2021
- 2021-09-07 CN CN202111041857.4A patent/CN113713096B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130315837A1 (en) * | 2012-02-23 | 2013-11-28 | Canon Kabushiki Kaisha | Dye-containing nanoparticle for photoacoustic contrast agent |
US20150037255A1 (en) * | 2013-07-30 | 2015-02-05 | Canon Kabushiki Kaisha | Phthalocyanine dye-containing contrast agent for photoacoustic imaging |
CN108940365A (zh) * | 2018-06-25 | 2018-12-07 | 山东大学 | 一种制备酞菁铁水溶性分散纳米粒子的方法 |
CN109260473A (zh) * | 2018-10-18 | 2019-01-25 | 河南大学 | 一种具有肿瘤靶向功能的卟啉纳米复合物及其制备方法和应用 |
WO2020205729A1 (en) * | 2019-03-29 | 2020-10-08 | The Brigham And Women's Hospital, Inc. | Targeted synergistic cancer immunotherapy |
Non-Patent Citations (2)
Title |
---|
纳米功能化酞菁复合物的合成及其光物理性质;陈秀琴;《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》;20160215(第2期);中文摘要、第51、53页 * |
陈秀琴.纳米功能化酞菁复合物的合成及其光物理性质.《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》.2016,(第2期),第B014-569页. * |
Also Published As
Publication number | Publication date |
---|---|
CN113713096A (zh) | 2021-11-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Jia et al. | Synthesis of carbon dots from Hypocrella bambusae for bimodel fluorescence/photoacoustic imaging-guided synergistic photodynamic/photothermal therapy of cancer | |
Mo et al. | Multifunctional phototheranostic nanoplatform based on polydopamine-manganese dioxide-IR780 iodide for effective magnetic resonance imaging-guided synergistic photodynamic/photothermal therapy | |
Fu et al. | Stimuli-responsive plasmonic assemblies and their biomedical applications | |
CN108434462B (zh) | 一种介孔聚多巴胺负载羰基锰的多功能纳米诊疗剂及其制备方法与应用 | |
Yang et al. | Recent advances in nanosized metal organic frameworks for drug delivery and tumor therapy | |
CN108671231B (zh) | 一种用于肿瘤光热增效治疗和超声成像的多功能纳米载体及制备方法 | |
CN109464677B (zh) | 一种用于肿瘤靶向诊疗的近红外光控纳米颗粒及制备方法 | |
CN105251420A (zh) | 一种多功能复合微球的制备方法 | |
CN108578696B (zh) | 一种脂质体微泡载金属-icg自组装复合体系 | |
CN107469079B (zh) | 一种t1-mri成像引导下的光动治疗剂制备方法 | |
Li et al. | Ultra-small gold nanoparticles self-assembled by gadolinium ions for enhanced photothermal/photodynamic liver cancer therapy | |
Zhao et al. | Gold nanorod-enhanced two-photon excitation fluorescence of conjugated oligomers for two-photon imaging guided photodynamic therapy | |
Chen et al. | Photosensitizer–conjugated Cu-In-S heterostructured nanorods for cancer targeted photothermal/photodynamic synergistic therapy | |
Panda et al. | PEG–PEI-modified gated N-doped mesoporous carbon nanospheres for pH/NIR light-triggered drug release and cancer phototherapy | |
CN113577306B (zh) | 一种双靶向、pH刺激响应的纳米粒子的制备及其在肿瘤诊疗中的应用 | |
CN104117074B (zh) | 一种基于聚吡咯复合物的治疗诊断制剂及其制备方法 | |
CN109420181A (zh) | 一种用于肿瘤荧光成像及光热/光动力治疗的多功能纳米粒子 | |
CN113713096B (zh) | 一种萘酞菁铜与Au复合材料及其制备方法和应用 | |
CN111110844A (zh) | 一种磁热触发自由基生成纳米材料的制备方法和应用 | |
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 | |
Xiang et al. | Functional terpyridyl iron complexes for in vivo photoacoustic imaging | |
Zahraie et al. | Pulsed sonodynamic therapy of melanoma cancer cells using nanoparticles of and mesoporous platinum | |
Gowtham et al. | Synthetic routes to theranostic applications of carbon-based quantum dots | |
Ye et al. | Developing gold nanotubes as photoacoustic contrast agents | |
CN107737945B (zh) | 一种复合纳米金颗粒的合成方法及应用 |
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 |