Endosome/lysosome-detained supramolecular nanogels as an efflux retarder and autophagy inhibitor for repeated photodynamic therapy of multidrug-resistant cancer.,Nanoscale Horizons

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Endosome/lysosome-detained supramolecular nanogels as an efflux retarder and autophagy inhibitor for repeated photodynamic therapy of multidrug-resistant cancer.
Nanoscale Horizons ( IF 8.0 ) Pub Date : 2019-10-22 , DOI: 10.1039/c9nh00643e
Xiaodong Zhang ₁ , Xiaokai Chen , Yuxin Guo , Hao-Ran Jia , Yao-Wen Jiang , Fu-Gen Wu

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The presence of drug efflux pumps and endo/lysosomal entrapment phenomena in multidrug-resistant cancer cells leads to insufficient and off-target accumulation of anticancer drugs in the cells, which severely reduces the drugs’ therapeutic efficacies. Here, we prepare a novel type of photosensitizer (PS)-loaded supramolecular nanogel, which can utilize the endo/lysosomal entrapment for enhanced photodynamic therapy (PDT) of multidrug-resistant cancer. The PS-loaded nanogels can elude the drug efflux pumps, and be markedly internalized by drug-resistant cancer cells through the endocytic pathway. With their pH-sensitive properties, the internalized nanogels can aggregate in the acidic endosomes/lysosomes, thus retarding their exocytosis from the cells. Moreover, the lysosomes of the nanogel-treated cells are severely damaged after irradiation, which inhibits the protective autophagy and improves the photodynamic therapeutic performance of the nanogels. Besides, the in vivo experiments show that the nanogels significantly prolong the tumor retention of the PSs, thus enabling multiple PDT treatments after a single drug injection.

中文翻译：

内吞/溶酶体保留的超分子纳米凝胶作为外排阻滞剂和自噬抑制剂，用于多药耐药性癌症的重复光动力治疗。

多药耐药性癌细胞中药物外排泵的存在和内/溶酶体截留现象导致抗癌药物在细胞中的积累不足和脱靶，这严重降低了药物的治疗效果。在这里，我们准备了一种新型的光敏剂（PS）超分子纳米凝胶，它可以利用内体/溶酶体包埋来增强对多药耐药性癌症的光动力疗法（PDT）。载有PS的纳米凝胶可逃避药物外排泵的作用，并被耐药性癌细胞通过内吞途径显着内在化。内在的纳米凝胶具有对pH敏感的特性，可以聚集在酸性内体/溶酶体中，从而阻止其从细胞中的胞吐作用。此外，纳米凝胶处理的细胞的溶酶体在照射后会受到严重破坏，抑制了保护性自噬并改善了纳米凝胶的光动力治疗性能。此外，体内实验表明，纳米凝胶可显着延长PSs的肿瘤保留时间，从而在单次药物注射后即可进行多种PDT治疗。

更新日期：2019-10-22

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