首页|键合光敏剂的铂基聚吡咯用于氧气增强的光动力治疗

键合光敏剂的铂基聚吡咯用于氧气增强的光动力治疗

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光动力治疗是一种具有临床前景的新兴癌症治疗方法,可以特异地在肿瘤部位发挥作用并且对人体的伤害较小,但是疏水性光敏剂小分子的毒性、肿瘤的乏氧微环境及纳米载药系统的生物降解性等影响了其抗肿瘤疗效和体内代谢清除。本文利用六氯铂酸作为新型氧化剂成功引发吡咯/氨基吡咯的氧化聚合,实现了其表面氨基功能化;进一步通过还原剂硼氢化钠还原纳米结构中铂酸阴离子为铂纳米簇,制得铂纳米簇掺杂的聚吡咯纳米粒子(platinum nanocluster-doped polypyrrole nanoparticles,PtPPy);最后通过酰胺键偶连光敏剂四(4-羧基苯基)卟吩[meso-tetra(4-carboxyphenyl)porphine,TCPP],获得递送TCPP的功能性纳米药物(PtPPy@T)。该纳米药物为球型结构,形态均匀,粒径为91。93±13。45 nm,zeta电位为-18。39±1。4 mV。实验证明,PtPPy@T可与肿瘤过表达的过氧化氢发生反应,产生大量的氧气,改善肿瘤乏氧微环境,同时为随后的光动力治疗提供充足的反应基板;使用658 nm激光照射肿瘤组织,激活PtPPy@T的光动力效应,催化氧气转化为单线态氧,从而引发肿瘤细胞的氧化损伤并诱导其凋亡;实验研究表明该PtPPy@T纳米药物在体内和体外都有较好的肿瘤抑制效果。所有动物实验均经中国医学科学院、北京协和医学院放射医学研究所机构动物护理和使用委员会批准(IRM/2-IACUC-2312-006)。
Platinum-based polypyrrole is used in oxygen-enhanced photodynamic therapy
Photodynamic therapy is an emerging cancer therapy with clinical prospects,which plays a specific role in the tumor site and causes less harm to the human body.However,the toxicity of small molecules of hydrophobic photosensitizer,the tumor hypoxia microenvironment,and the biodegradability of nano-carrier systems affect its antitumor efficacy and metabolic clearance in vivo.In this paper,hexachloroplatinic acid was used as a novel oxidizing agent to initiate oxidative polymerization of pyrrole/amino pyrrole to achieve the amino functionalization;further reduced platinum acid anion in the nanostructures into platinum nanoclusters by sodium borohydride as a reducing agent to fabricate platinum nanocluster-doped polypyrrole nanoparticles(PtPPy);and finally,this functional nanoparticles delivering messo-tetra(4-carboxyphenyl)porphine(TCPP)were obtained by amide-bonded coupling of photosensitizers TCPP drug(PtPPy@T).The nanomedicine had a spherical structure,uniform morphology,a particle size of 91.93±13.45 nm,and a zeta potential of-18.39±1.4 mV.Experiments demonstrated that PtPPy@T could react with hydrogen peroxide overexpressed in the tumor to generate a large amount of oxygen,which could relieve the tumor hypoxia microenvironment,and at the same time,provided a sufficient substrate for the subsequent PDT;using 658 nm laser irradiation,the photodynamic effect of PtPPy@T was activated,which catalyzed the conversion of oxygen to singlet oxygen,thus triggering oxidative damage and inducing apoptosis in tumor cells;experimental studies showed that the PtPPy@T nanomedicine had a better tumor inhibitory effect in vivo and in vitro.All animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Radiological Medicine,Chinese Academy of Medical Sciences and Peking Union Medical College(IRM/2-IACUC-2312-006).

polypyrrolenano-drugphotodynamic therapytumor hypoxiaoxidative damage

张越、李晗玥、曾伟健、梅林、陈大全

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烟台大学药学院,分子药理和药物评价教育部重点实验室(烟台大学),新型制剂与生物技术药物研究山东省高校协同创新中心,山东烟台 264005

中国医学科学院、北京协和医学院生物医学工程研究所,先进医用材料与医疗器械全国重点实验室,天津市生物医学材料重点实验室,天津 300192

宁波大学科学技术学院,浙江宁波 315212

聚吡咯 纳米药物 光动力治疗 肿瘤乏氧 氧化损伤

国家重点研发计划政府间国际科技创新合作重点专项天津市杰出青年基金项目

2022YFE013980022JCJQJC00120

2024

药学学报
中国药学会 中国医学科学院药物研究所

药学学报

CSTPCD北大核心
影响因子:1.274
ISSN:0513-4870
年,卷(期):2024.59(7)
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