Synergistic innate-adaptive chemo-immunotherapy through a high-payload nanoplatform
The synergistic strategy combining chemotherapy and immunotherapy has recently demonstrated significant promise in cancer treatment. However, the substantial physicochemical disparities between chemotherapeutic agents and small-molecule immune adjuvants pose considerable challenges for co-delivery strategies. In this study, we designed a reactive oxygen species-responsive paclitaxel prodrug, PTX-PBA, which markedly enhanced drug encapsulation stability and dual-drug loading efficiency by various polymeric delivery systems. The resultant nanosystem (NanoPR) exhibited excellent physicochemical properties and ROS-triggered release profiles, effectively inducing immunogenic cell death in tumor cells while promoting dendritic cell maturation and CD8+ T cells activation. In murine models of 4T1 breast cancer and CT26 colon carcinoma, NanoPR achieved significant tumor growth inhibition and elicited durable immune memory responses. Collectively, this work provides an innovative molecular design strategy for the co-delivery of chemotherapeutics and immunomodulators, offering a robust foundation for the clinical translation of chemo-immunotherapy.