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首页> 外文期刊>Biomaterials Science >Encapsulating an acid-activatable phthalocyanine-doxorubicin conjugate and the hypoxia-sensitive tirapazamine in polymeric micelles for multimodal cancer therapy
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Encapsulating an acid-activatable phthalocyanine-doxorubicin conjugate and the hypoxia-sensitive tirapazamine in polymeric micelles for multimodal cancer therapy

机译：在聚合物胶束上包封酸活化的酞菁 - 多柔比星和缺氧敏感的二拉唑胺以进行多式联癌疗法

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摘要

A zinc(ii) phthalocyanine (ZnPc) was conjugated to doxorubicin (Dox) via an acid-labile hydrazone linker. The resulting ZnPc-Dox conjugate was then encapsulated into polymeric micelles formed through self-assembly of a block copolymer of poly(ethylene glycol) and poly(d,l-lactide) both in the absence and presence of the hypoxia-activated prodrug tirapazamine (TPZ) to give ZnPc-Dox@micelles and ZnPc-Dox/TPZ@micelles respectively. These polymeric micelles exhibited an excellent stability in aqueous media, but underwent disassembly in an acidic environment. Upon internalisation into HT29 human colorectal carcinoma cells, fluorescence due to ZnPc and Dox could be observed in the cytoplasm and nucleus respectively for both nanosystems. This observation suggested the disassembly of the polymeric micelles and the cleavage of the hydrazone linker in ZnPc-Dox in the acidic intracellular compartments. These micelles were slightly cytotoxic against HT29 cells in the dark due to the chemotherapeutic effect of Dox and/or TPZ. Upon light irradiation, ZnPc-Dox@micelles showed higher cytotoxicity. The IC50 value under a normoxic condition (0.35 mu M based on ZnPc-Dox) was significantly lower than that under hypoxia (>1 mu M). With an additional therapeutic component, ZnPc-Dox/TPZ@micelles exhibited higher photocytotoxicity with IC50 values of 0.20 mu M and 0.78 mu M under normoxia and hypoxia respectively. It is believed that the photodynamic action of this nanosystem consumed the intracellular oxygen and hence triggered the hypoxia-mediated chemotherapeutic action of TPZ. The multimodal antitumor effects of these polymeric micelles were also validated on HT29 tumour-bearing nude mice.
机译：将锌（II）酞菁（ZnPC）通过酸不稳定的腙接头与多柔比星（DOX）缀合。然后将得到的ZnPC-DOX缀合物包封成通过在缺氧活化的前药Tirapazamine（ TPZ）分别给出ZnPC-Dox @胶束和ZnPC-Dox / TPZ @胶束。这些聚合物胶束在含水介质中表现出优异的稳定性，而是在酸性环境中进行拆卸。在内化到HT29人结肠直肠癌细胞中，分别在纳米系统中分别观察到由于ZnPC和DOX引起的荧光分别用于纳米系统。该观察结果表明聚合物胶束的拆卸和含有酰肼接头在酸性细胞内隔室中的ZnPC-Dox中的裂解。由于DOX和/或TPZ的化学治疗效果，这些胶束在黑暗中对HT29细胞略微细胞毒性。在光线照射时，ZnPC-Dox @胶束显示出更高的细胞毒性。在常氧条件下的IC 50值（基于ZnPC-DOX的0.35μm）显着低于缺氧（>1μm）下的含量。通过额外的治疗组分，ZnPC-Dox / TPZ @胶束分别在常氧和缺氧下具有0.20μm和0.78μm的IC 50值更高的光致毒性。据信，该纳米系统的光动力动力作用消耗细胞内氧，因此引发了TPZ的缺氧介导的化学治疗作用。在HT29携带的HT29肿瘤裸鼠上还验证了这些聚合物胶束的多模式抗肿瘤效应。

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  • 来源
    《Biomaterials Science》 |2021年第14期|共16页
  • 作者

    Guo Xuejiao; Jin Honglin; Lo Pui-Chi;

  • 作者单位

    City Univ Hong Kong Dept Biomed Sci Kowloon Tat Chee Ave Hong Kong Peoples R China;

    Huazhong Univ Sci &

    Technol Tongji Med Coll Union Hosp Canc Ctr Wuhan 430022 Peoples R China;

    City Univ Hong Kong Dept Biomed Sci Kowloon Tat Chee Ave Hong Kong Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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