A single-component zinc-doped ferrite nanoplatform for MRI/PAI-guided magneto- mechanical/photothermal synergistic therapy against triple-negative breast cancer and lung metastasis

Triple-negative breast cancer (TNBC) poses significant therapeutic challenges due to its aggressive phenotype, high metastatic potential, and lack of targeted treatment options. Herein, we report zinc-doped ferrite magnetic nanoparticles (Zn0.2Fe2.8O4 MNPs) as a single-component theranostic platform for magnetic resonance (MRI)/photoacoustic (PAI) dual-mode imaging-guided synergistic therapy that enhances TNBC treatment and suppression metastasis. Through optimization of Zn2+ doping content, the NPs exhibit superior magnetic and optical properties, allowing high- performance T2-weighted MRI and high-resolution PAI under 808 nm laser irradiation, thereby facilitating detailed visualization of tumor vasculature. The same platform enables highly effective photothermal therapy (PTT) under 1064 nm laser excitation, leveraging deep-tissue penetration and a higher maximum permissible exposure. Moreover, the NPs generate localized magneto-mechanical forces (MMF) that disrupted cytoskeletal integrity, and notably suppressed metastatic progression by reversing epithelial-mesenchymal transition (EMT). In vivo studies demonstrate complete tumor eradication and significant inhibition of lung metastasis in TNBC models. This work presents a simple yet powerful strategy that integrates multimodal imaging with synergistic therapeutic functions within a single agent, offering a clinically translatable approach for combating TNBC and its metastatic recurrence.