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Tumor-mediated shape-transformable nanogels with pH/redox/enzymatic-sensitivity for anticancer therapy.
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-05-06 , DOI: 10.1039/d0tb00143k Dong Zhou 1 , Sainan Liu 1 , Yongjun Hu 2 , Shiwei Yang 2 , Bing Zhao 1 , Kaikai Zheng 1 , Yuhong Zhang 1 , Peixin He 1 , Guoyan Mo 2 , Yulin Li 3
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2020-05-06 , DOI: 10.1039/d0tb00143k Dong Zhou 1 , Sainan Liu 1 , Yongjun Hu 2 , Shiwei Yang 2 , Bing Zhao 1 , Kaikai Zheng 1 , Yuhong Zhang 1 , Peixin He 1 , Guoyan Mo 2 , Yulin Li 3
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Lack of sufficient tumor penetration of the current nanomedicines is a major reason limiting their clinical success in cancer therapy. In this work, we aimed at the development of a novel biodegradable nanoplatform for the selective and controlled delivery of anticancer agents, with improved tumor permeability and the ability to release ultrasmall nanovesicles in the tumor microenvironment. To this end, positively charged nanogels were obtained through the double-crosslinking of chitosan with an ionic physical gelator and a disulfide-containing chemical crosslinker. After conjugation to an anionic oligomer, the cationic nanogels were transformed into negatively charged nanocarriers (CTCP), enabling effective encapsulation of the cationic anticancer agent doxorubicin (DOX) to generate a biodegradable nanomedicine (DOX@CTCP). DOX@CTCP could maintain sustained DOX release and decreased DOX toxicity. Upon arrival at the tumor tissue, the reductive and lysozyme-high microenvironment drives the cleavage of the nanomedicine to release DOX-carrying nanoblocks of smaller size, which together with their acidic-protonable feature achieves an effective therapeutic delivery into cancer cells. The nanomedicine described here showed excellent biocompatibility/biosafety and enhanced in vivo antitumor efficacy.
中文翻译：
具有pH /氧化还原/酶敏感性的肿瘤介导的形状可转换纳米凝胶，用于抗癌治疗。
当前的纳米药物缺乏足够的肿瘤渗透性是限制其在癌症治疗中临床成功的主要原因。在这项工作中，我们旨在开发一种新型的可生物降解的纳米平台，用于选择性和受控地输送抗癌药物，具有改善的肿瘤通透性和在肿瘤微环境中释放超小型纳米囊泡的能力。为此，通过将壳聚糖与离子物理胶凝剂和含二硫化物的化学交联剂进行双交联，可获得带正电的纳米凝胶。与阴离子低聚物缀合后，阳离子纳米凝胶被转变为带负电荷的纳米载体（CTCP），从而使阳离子抗癌剂阿霉素（DOX）得以有效封装，从而产生了可生物降解的纳米药物（DOX @ CTCP）。DOX @ CTCP可以维持持续的DOX释放并降低DOX毒性。到达肿瘤组织后，具有还原性和溶菌酶高的微环境驱动纳米药物的裂解，释放出较小尺寸的带有DOX的纳米块，这些纳米块连同其酸性质子化功能一起可以有效地将治疗性药物传递到癌细胞中。本文所述的纳米药物显示出优异的生物相容性/生物安全性并增强了体内抗肿瘤功效。
更新日期：2020-02-27
中文翻译：
具有pH /氧化还原/酶敏感性的肿瘤介导的形状可转换纳米凝胶，用于抗癌治疗。
当前的纳米药物缺乏足够的肿瘤渗透性是限制其在癌症治疗中临床成功的主要原因。在这项工作中，我们旨在开发一种新型的可生物降解的纳米平台，用于选择性和受控地输送抗癌药物，具有改善的肿瘤通透性和在肿瘤微环境中释放超小型纳米囊泡的能力。为此，通过将壳聚糖与离子物理胶凝剂和含二硫化物的化学交联剂进行双交联，可获得带正电的纳米凝胶。与阴离子低聚物缀合后，阳离子纳米凝胶被转变为带负电荷的纳米载体（CTCP），从而使阳离子抗癌剂阿霉素（DOX）得以有效封装，从而产生了可生物降解的纳米药物（DOX @ CTCP）。DOX @ CTCP可以维持持续的DOX释放并降低DOX毒性。到达肿瘤组织后，具有还原性和溶菌酶高的微环境驱动纳米药物的裂解，释放出较小尺寸的带有DOX的纳米块，这些纳米块连同其酸性质子化功能一起可以有效地将治疗性药物传递到癌细胞中。本文所述的纳米药物显示出优异的生物相容性/生物安全性并增强了体内抗肿瘤功效。
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