pH响应型原位抗原捕获与胞质递送系统协同诱导系统性抗肿瘤免疫

Abstract

In situ cancer vaccines hold strong potential for addressing tumor heterogeneity by using the patient’s own tumor as a personalized antigen source. However, their efficacy remains limited by insufficient antigen capture and inefficient cytosolic delivery. Here, we report an in situ antigen capture and delivery platform, DOX/PDiT@Gel, in which the pH-responsive function is provided by the polymer PDiT, while the hydrogel serves as a local retention matrix. In this system, doxorubicin (DOX) and a cationic polymer, PEG-DIPAMA-TAT (PDiT), are co-encapsulated within an oxidized dextran/carboxymethyl chitosan hydrogel. DOX induces immunogenic cell death, releasing diverse tumor antigens, while PDiT captures these antigens in situ via electrostatic interactions and promotes endo/lysosomal escape under acidic conditions. The hydrogel allows localized delivery of the therapeutic components at the postoperative tumor site. In vitro studies showed that PDiT markedly promoted antigen internalization, cross-presentation, and dendritic cell maturation. In murine models of postoperative recurrence and bilateral breast tumors, local treatment with DOX/PDiT@Gel inhibited the growth of both recurrent and distant tumors, together with stronger dendritic cell activation and enhanced memory T cell responses. Overall, this platform effectively amplifies antitumor immunity and offers a versatile strategy for personalized cancer immunotherapy. Graphical