PCN-224 engineered self-amplifying nanoplatform for TME responsive multimodal imaging and in situ vaccinated combined therapy

Breast cancer remains a major clinical challenge due to its high incidence, tumor heterogeneity, hypoxia, and limited treatment specificity. In this study, we developed PMDH, a six-in-one integrated nanoplatform for targeted multimodal imaging and combined therapy. PMDH was constructed by sequentially coating a MnO 2 shell on PCN–224, loading doxorubicin (DOX), and conjugating hyaluronic acid (HA). The system features complementary tumor microenvironment (TME) responsive imaging modalities, including fluorescence imaging, magnetic resonance imaging, and photoacoustic imaging for precise diagnostics. Therapeutically, PMDH enables controlled DOX release for chemotherapy, self-enhanced photodynamic therapy (PDT) through intratumoral oxygen generation, and PDT-triggered immunotherapy. These integrated capabilities were comprehensively validated through in vitro and in vivo studies, underscoring PMDH’s potential as a versatile and precise platform for oncology treatment.