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    肖潮, 田佳, 刘峰, 张显杨, 王廷虎, 许立人, 顾邯沙, 张伟安. 基于pH响应两亲性卟啉嵌段共聚物的光动力与化学联合治疗[J]. 华东理工大学学报(自然科学版), 2020, 46(2): 208-218. DOI: 10.14135/j.cnki.1006-3080.20190128001
    引用本文: 肖潮, 田佳, 刘峰, 张显杨, 王廷虎, 许立人, 顾邯沙, 张伟安. 基于pH响应两亲性卟啉嵌段共聚物的光动力与化学联合治疗[J]. 华东理工大学学报(自然科学版), 2020, 46(2): 208-218. DOI: 10.14135/j.cnki.1006-3080.20190128001
    XIAO Chao, TIAN Jia, LIU Feng, ZHANG Xianyang, WANG Tinghu, XU Liren, GU Hansha, ZHANG Weian. Combinational Photodynamic Therapy and Chemotherapy Based on an Amphiphilic pH-Responsive Porphyrin-Containing Block Copolymer[J]. Journal of East China University of Science and Technology, 2020, 46(2): 208-218. DOI: 10.14135/j.cnki.1006-3080.20190128001
    Citation: XIAO Chao, TIAN Jia, LIU Feng, ZHANG Xianyang, WANG Tinghu, XU Liren, GU Hansha, ZHANG Weian. Combinational Photodynamic Therapy and Chemotherapy Based on an Amphiphilic pH-Responsive Porphyrin-Containing Block Copolymer[J]. Journal of East China University of Science and Technology, 2020, 46(2): 208-218. DOI: 10.14135/j.cnki.1006-3080.20190128001

    基于pH响应两亲性卟啉嵌段共聚物的光动力与化学联合治疗

    Combinational Photodynamic Therapy and Chemotherapy Based on an Amphiphilic pH-Responsive Porphyrin-Containing Block Copolymer

    • 摘要: 光动力疗法(PDT)是癌症治疗的重要研究方向之一。通过将可逆加成-断裂链转移(RAFT)聚合与点击化学偶联反应相结合构建了一种两亲性嵌段共聚物聚乙二醇-聚甲基丙烯酸二异丙基氨基乙酯-四苯基卟啉(PEG-PDPA-TPP),该共聚物的中间连接有一个可作为光动力疗法中光敏剂(PS)的四苯基卟啉(TPP)基元。这种在连接点带有卟啉的两亲性pH响应性嵌段共聚物可以在水溶液中自组装成球形胶束,并用作药物释放平台以及大分子光敏剂。TPP部分会相对规则地分布在球形胶束的核周围,降低卟啉单元之间的聚集,并减少聚集引起的光敏剂自猝灭效应,从而提高单线态氧量子产率。因此,这种基于pH响应的含TPP的嵌段共聚物的药物释放平台能够为癌症治疗提供一种新策略。

       

      Abstract: Nowadays, photodynamic therapy(PDT) has become one of the promising and important cancer therapies. 5, 10, 15, 20-Tetraphenyl porphyrin(TPP), a unique and promising photosensitizer which can convert triplet oxygen(3O2) into singlet oxygen(1O2) after laser illumination, can be used to kill cancer cells. Due to the strong hydrophobicity of porphyrin molecules, porphyrins always need the physical encapsulation by different vehicles. However, the general physical encapsulation not only makes it difficult to quantify the loaded porphyrin content accurately, but also causes aggregation effects after the intracellular release, leading to a compromised PDT effect. Herein, we developed a NIR-triggered pH-responsive amphiphilic block copolymer as to serve as the photosensitizer and drug delivery system(DDS) for the combination of PDT therapy and chemotherapy. The well-defined block copolymer was composed of hydrophilic poly(ethylene glycol)(PEG) block, hydrophobic poly((diisopropylamino)ethyl methacrylate)(PDPA) block and a TPP unit at the junction point between PEG and PDPA. Such a copolymer was synthesized by the combination of RAFT polymerization and click chemistry. The amphiphilic pH-responsive block copolymer(PEG-PDPA-TPP) can self-assemble into spherical micelles in aqueous solution and perform as a perfect drug release platform. It is worthy to notice that the well-designed chemical structure of PEG-PDPA-TPP with TPP at the junction point leads to a relatively regular arrangement of TPP moieties between the hydrophobic and hydrophilic blocks instead of aggregating together, which can reduce the aggregation-induced quenching effect of the photosensitizers, thereby increasing the quantum yield of singlet oxygen. Meanwhile, the Doxorubicin(DOX)-loaded PEG-PDPA-TPP nanoparticles will dissociate under weak acidic conditions and release the drug after entering the cells by endocytosis. Therefore, this pH-responsive TPP-containing block copolymer provides a new strategy for cancer treatment.

       

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