Near-Infrared-Triggered “Bridge-and-Attack” Strategy via a Bioinspired Copper–Polyphenol Nanoarchitectonics Platform for Vascular Normalization-Enhanced Cuproptosis-Immunotherapy of Triple-Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) presents formidable treatment barriers due to dysfunctional vasculature and an immunosuppressive microenvironment. To address these challenges, we engineered a bioinspired near-infrared (NIR)-responsive copper–polyphenol nanoplatform, SCP, to implement a NIR-triggered “bridge-and-attack” therapeutic strategy. This nanoassembly was constructed through the coordination of salvianolic acid B (SAB) with copper ions and further stabilized by a polydopamine (PDA) shell. Upon NIR irradiation, SAB and Cu2+ were co-released from SCP, enabling simultaneous vascular remodeling and tumor cell killing. The released SAB promoted vascular normalization, increasing pericyte coverage to 51.6% and alleviating tumor hypoxia, thereby facilitating intratumoral penetration and immune-cell infiltration. Meanwhile, released Cu2+, together with PDA-mediated photothermal activation, induced cuproptosis and immunogenic cell death (ICD). This combined remodeling of the tumor microenvironment enhanced CD8+ T cell infiltration and achieved a tumor inhibition rate of 88.5% in 4T1 tumor-bearing mice with favorable systemic biosafety. Overall, this interfacial nanomaterial design integrates vascular normalization, photothermal-enhanced cuproptosis, and immunotherapy, providing a promising materials-based strategy for TNBC treatment.