Platelet Activation-Induced In Situ Trapping Metastatic Tumor Cells Strategy for Post-Surgery Tumor Recurrence Immunochemotherapy.

Abstract

The reasons for the high recurrence and metastasis after triple-negative breast cancer (TNBC) surgery are the potential presence of micrometastases and disseminated tumor cells in the circulation, as well as the immunosuppressive microenvironment caused by the surgery. To address these issues, this work proposed a platelets (PLTs) based hydrogel delivery system for immuno-chemotherapy, (IL-12+NP_D-PLT)@dAlg. To utilize the targeting ability of PLTs toward tumor cells and maintain the activity of PLTs, doxorubicin-loaded nanoparticles (NP_D) were attached on the surface of PTLs (NP_D-PLT). Under the conditions of the post-surgical tumor microenvironment (TME), these PTLs responsively released small-sized drug-loaded vesicles (NP_D-PMP) trapping metastatic tumor cells, inducing immunogenic cell death (ICD) of tumor cells. Additionally, immunomodulatory drugs, IL-12, was combined in the hydrogel to synergistically activate CD8⁺ T cells within the body and induce the polarization of tumor-associated macrophages (TAMs) toward M1 cells, thereby improving the immunosuppressive microenvironment post-surgery. In a 4T1 tumor recurrence and metastasis mouse model, (IL-12+NP_D-PLT)@dAlg has shown effective inhibition of tumor recurrence and metastasis, reversing the tumor immune environment, and prolonging survival.