A Honeycomb‐Like Bismuth/Manganese Oxide Nanoparticle with Mutual Reinforcement of Internal and External Response for Triple‐Negative Breast Cancer Targeted Therapy

Abstract

Triple-negative breast cancer (TNBC) exhibits aggressive behavior and high levels of metastasis owing to its complex heterogeneous structure and lack of specific receptors. Here, tumor cell membrane (CM)-coated bismuth/manganese oxide nanoparticles (NPs) with high indocyanine green (ICG) payload up to 50.6 wt% (mBMNI NPs) for targeted TNBC therapy are constructed. The extra-high drug load Bi@Bi₂ O₃ @MnO_x NPs (honey-comb like structure) are formed by Kirkendall effect and electrostatic attraction. After modified with CM, they can home into tumor sites precisely, where they respond to internal overexpressed glutathione (GSH), releasing Mn²⁺ for chemodynamic therapy (CDT) with GSH depletion, while H₂ O₂ degrades into O₂ enabling relief of tumor hypoxia. In response to external near-infrared irradiation, mBMNI NPs intelligently generate vigorous heat and single oxygen (¹ O₂ ) for photothermal therapy (PTT) and photodynamic therapy (PDT) owing to high load. Importantly, O₂ production and GSH consumption during the internal response reinforce external PDT, while the heat generated through PTT during the external response promotes internal CDT. The honeycomb-like structure with high ICG load and mutual reinforcement between internal and external response results in excellent therapeutic effects against TNBC.