A violet phosphorus-engineered immunogel for combating TNBC progression via tumor microenvironment remodeling

In-situ delivery-based immunotherapy provides a promising strategy for precisely remodeling tumor microenvironment (TME) to inhibit the progression and metastasis of triple-negative breast cancer (TNBC). Herein, a multifunctional photosensitive nanoplatform, violet phosphorus nanosheet (VPN), was applied to co-load methylene blue (MB) and doxorubicin (DOX). Subsequently, an immunogel (MDVa@PM gel) was spontaneously formed by incorporating the above VPN-based nanocomposite and anti-PD-L1 antibody (aPD-L1) into polymetformin (PM)-generated hydrogel. The injectable and weak-acid sensitive characteristics of MDVa@PM gel enabled its intratumoral administration through syringe and facilitated responsive drug release at local tumor site. Benefitting from the synergistic effects of photodynamic therapy (PDT)-induced immunoactivation mediated by VPN and MB, immune checkpoint blockade therapy (ICBT) via aPD-L1, and the immunomodulatory activities of PM and MB, MDVa@PM gel effectively remodeled the TME from an immunosuppressive to an immune-activated state. This enhanced immunity further cooperated with the direct tumoricidal effects of PM, DOX, and PDT, leading to improved therapeutic efficacy against TNBC. Overall, this immunogel combined with PDT not only inhibited both primary and abscopal tumors progression, but also established long-term immune memory to suppress metastasis, offering a viable therapeutic strategy against TNBC across different stages.