近年来，pH响应型纳米凝胶在癌症治疗中扮演着越来越重要的角色。本研究着重设计和开发基于海藻酸的pH响应型纳米凝胶，以实现依托泊苷(etoposide, Et)的控释，并提高其亲水性。通过微波诱导方法，将海藻酸(alginate, ALG)与2-羟丙基甲基丙烯酰胺(hydroxypropyl methacrylamide, HPMA)接枝，并通过1H/13C NMR和FTIR技术验证了接枝共聚物(ALG-g-PHPMA)的化学结构。采用乳化法制备了ALG-g-PHPMA和抗癌药物载药的ALG-g-PHPMA@Et纳米凝胶，通过FTIR、TG/DSC、AFM/TEM、BET和DLS分析对其结构进行了表征。ALG-g-PHPMA纳米凝胶显示出良好的药物封装效率（79.60%），呈现出pH依赖的释放特性，并与ALG纳米凝胶相比，在体外加速释放Et。热分析和BET分析揭示了海藻酸纳米凝胶的增强稳定性、表面积和孔隙体积。将PHPMA链接枝到海藻酸上改变了ALG纳米凝胶的表面拓扑结构，导致表面粗糙度降低。此外，细胞毒性实验显示ALG-g-PHPMA共聚物及其纳米凝胶具有较高的生物相容性。ALG-g-PHPMA@Et纳米凝胶对肺癌（H1299）细胞表现出比游离etoposide更高的抗癌效果。这些结果表明，ALG-g-PHPMA纳米凝胶可以作为一种pH依赖的纳米平台应用于抗癌药物的传递。版权所有©2023 Elsevier B.V.发布。

Recently, pH-responsive nanogels are playing progressively important roles in cancer treatment. The present study focuses on designing and developing pH-responsive alginate-based nanogels to achieve a controlled release of etoposide (Et) while enhancing its hydrophilicity. Alginate (ALG) is grafted with 2-hydroxypropyl methacrylamide (HPMA) through a microwave-supported method, and the chemical structure of the graft copolymer (ALG-g-PHPMA) was verified by 1H/13C NMR and FTIR techniques. The ALG-g-PHPMA and anticancer drug-loaded ALG-g-PHPMA@Et nanogels were obtained using an emulsion method, and their structures were characterized through FTIR, TG/DSC, AFM/TEM, BET, and DLS analyses. The ALG-g-PHPMA nanogels demonstrated a good drug encapsulation efficiency (79.60 %), displaying a pH-dependent release profile and an in vitro accelerated release of Et compared to the ALG nanogels. Thermal and BET analyses revealed enhanced stability, surface area, and porosity volume of the alginate nanogels. The grafting of PHPMA chains onto alginate altered the surface topology of the ALG nanogels, resulting in lower surface roughness. Furthermore, cytotoxicity tests showed the high biocompatibility of the ALG-g-PHPMA copolymer and its nanogels. The ALG-g-PHPMA@Et nanogels exhibited a higher anticancer effect on lung cancer (H1299) cells than free etoposide. These results suggest that the ALG-g-PHPMA nanogels can be applied as a pH-dependent nanoplatform for delivering anticancer drugs.Copyright © 2023. Published by Elsevier B.V.