A novel strategy for the preparation of dual-responsive prodrug nanogels was proposed by Diels-Alder reaction. Firstly, poly(styrene- alt -maleic anhydride) copolymers were functionalized with furfuryl amine and hydrazine in a simple one-pot reaction. Secondly, doxorubicin (DOX) was further incorporated to copolymer via hydrazone linkage in the presence of dithiobismaleimidoethane as a cross-linking agent resulted in prodrug nanogels. The prodrug nanogels were stable under physiological condition while the disintegration of nanogels was taken place and DOX released rapidly in the redox medium. The prodrug nanogels presented strong toxicity towards HepG2 cell line, whereas they had almost no inhibition in HEK293 normal cell line. The results suggest that DOX conjugate-based nanogels would be a potential candidate for efficient drug nanocarrier. Graphical abstract

中文翻译：

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通过 Diels-Alder 反应的双响应前药纳米凝胶一步法用于药物递送

Diels-Alder反应提出了一种制备双响应前药纳米凝胶的新策略。首先，聚（苯乙烯-alt-马来酸酐）共聚物在简单的一锅反应中用糠胺和肼官能化。其次，在作为交联剂的二硫代双马来酰亚胺乙烷存在下，通过腙键将阿霉素（DOX）进一步掺入共聚物中，得到前药纳米凝胶。前药纳米凝胶在生理条件下是稳定的，而纳米凝胶发生崩解，DOX 在氧化还原介质中迅速释放。前药纳米凝胶对 HepG2 细胞系具有很强的毒性，而它们对 HEK293 正常细胞系几乎没有抑制作用。结果表明，基于 DOX 缀合物的纳米凝胶将成为有效药物纳米载体的潜在候选者。