pH-Responsive drug vehicles targeting the specific extracellular pH of tumors have served as potent tools to overcome the limitation (e.g., low tumor seletivity) in antitumor drug delivery system. Here, we describe the advantage of pH-responsive extracellular vesicles (HDEA@EVs) containing the hyaluronic acid grafted with 3-(diethylamino)propylamine (HDEA) and a model antitumor drug, doxorubicin (DOX). We demonstrated their physicochemical characteristics through in vitro cell endocytosis, in vitro tumor cell toxicity, in vivo biodistribution, and in vivo tumor regression efficacy experiments. Because the HDEA@EVs efficiently responded to extracellular tumor pH (pH 6.5) and actively bound to CD44 receptors on HCT-116 tumor cells, the EVs selectively inhibited CD44+ tumor cell growth in vitro, and CD44+ tumor development in vivo. From these results, we conclude that HDEA@EVs can help in designing effective strategies for pharmacologic intervention in tumor therapy.

靶向肿瘤特定细胞外pH的pH响应性药物载体已成为克服抗肿瘤药物递送系统中的局限性（例如，低的肿瘤易分离性）的有效工具。在这里，我们描述了pH响应的细胞外囊泡（HDEA @ EVs）的优势，该囊泡包含嫁接了3-（二乙氨基）丙胺（HDEA）和模型抗肿瘤药阿霉素（DOX）的透明质酸。我们通过体外细胞内吞作用，体外肿瘤细胞毒性，体内生物分布和体内实验证明了它们的理化特性。肿瘤消退功效实验。由于HDEA @ EV能够有效响应细胞外肿瘤pH（pH 6.5）并主动结合HCT-116肿瘤细胞上的CD44受体，因此EV在体外选择性抑制CD44 +肿瘤细胞的生长，并在体内抑制CD44 +肿瘤的发展。从这些结果，我们得出结论，HDEA @ EVs可以帮助设计有效的肿瘤治疗药物干预策略。