Abstract

Here we demonstrate a type of pH and redox dual-responsive micelles, which were self-assembled in aqueous solution by an amphiphilic polymer, methoxypoly(ethylene glycol)-cystamine-poly(L-glutamic acid)-imidazole (mPEG-SS-PGA-IM). Considering tumor cells or tissues exhibiting low pH values and high glutathione (GSH) concentration, mPEG-SS-PGA-IM micelles possessed the charge conversion at pH of tumor tissues, which can facilitate cellular uptake of tumor cells. Furthermore, mPEG-SS-PGA-IM micelles can escape from endo/lysosomes based on the proton sponge effect, following degraded by higher concentration of GSH in cytoplasm. CLSM images of HCT116 cells indicated that mPEG-SS-PGA-IM micelles can escape from endo/lysosomes and enter cytoplasm. MTT assay showed that (paclitaxel) PTX-loaded mPEG-SS-PGA-IM micelles had higher cytotoxicity against HCT116 cells compared with PTX-loaded mPEG-PBLG and mPEG-SS-PBLG micelles. These results indicated that these mPEG-SS-PGA-IM micelles, as novel and effective pH- and redox-responsive nanocarriers, have great potential to both improve drug targeting efficiency while also enhancing the antitumor efficacy of PTX.

摘要

在这里，我们展示了一种 pH 和氧化还原双响应胶束，它们通过两亲聚合物甲氧基聚（乙二醇）-胱胺-聚（L-谷氨酸）-咪唑（mPEG-SS-PGA）在水溶液中自组装-我是）。考虑到肿瘤细胞或组织表现出低 pH 值和高谷胱甘肽 (GSH) 浓度，mPEG-SS-PGA-IM 胶束在肿瘤组织的 pH 值下具有电荷转换，可以促进细胞对肿瘤细胞的摄取。此外，mPEG-SS-PGA-IM 胶束可以基于质子海绵效应从内/溶酶体中逃逸，随后被细胞质中较高浓度的 GSH 降解。HCT116 细胞的 CLSM 图像表明 mPEG-SS-PGA-IM 胶束可以从内/溶酶体逃逸并进入细胞质。MTT 测定表明，与负载 PTX 的 mPEG-PBLG 和 mPEG-SS-PBLG 胶束相比，（紫杉醇）负载 PTX 的 mPEG-SS-PGA-IM 胶束对 HCT116 细胞具有更高的细胞毒性。这些结果表明，这些 mPEG-SS-PGA-IM 胶束作为新型有效的 pH 和氧化还原响应纳米载体，在提高药物靶向效率和增强 PTX 的抗肿瘤功效方面具有巨大潜力。