Smart Tumor Oxygen Supply Strategy Enables Dual-Modality Fluorescence/MR Imaging and Synergistic Therapy of Triple-Negative Breast Cancer.

Abstract

Breast cancer progression is closely associated with hypoxia, which severely limits the efficacy of conventional therapy. In addition, the lack of real-time imaging hampers accurate monitoring of therapeutic processes, further reducing treatment precision and efficacy. Here, the rational design of a multifunctional nanoplatform that integrates hypoxia relief, dual-modality imaging, and synergistic therapy to overcome these barriers is reported. Mesoporous polydopamine nanoparticles are engineered and sequentially functionalized with the sonosensitizer chlorin e6 (Ce6), oxygen-generating manganese dioxide, and the targeting antibody cetuximab, yielding MPDA-Ce6@MnO₂-C225 (MCMC NPs). This construct exhibits a uniform nanoflower-like architecture, high Ce6 encapsulation efficiency, and robust oxygen supply capacity. By simultaneously enhancing reactive oxygen species generation and chemodynamic activity, MCMC NPs achieve potent SDT/CDT synergy under ultrasound activation. Importantly, they provide sensitive dual-modality fluorescence and magnetic resonance (MR) imaging, enabling real-time monitoring of nanoparticle distribution and therapeutic response. In vitro studies confirm excellent biocompatibility, targeted uptake by 4T1 breast cancer cells, and significant MRI signal enhancement. In vivo, MCMC NPs effectively alleviate tumor hypoxia, markedly suppress tumor growth, and prolong therapeutic response. This study establishes MCMC NPs as a versatile nanotheranostic platform that integrates imaging with oxygen-augmented SDT/CDT, offering a promising strategy for precise and effective breast cancer treatment.