Photothermal therapy (PTT) converts light to heat, offering a minimally invasive tumor treatment option. However, its efficacy for triple-negative breast cancer (TNBC) is limited by nanoparticle non-specificity and immunosuppression from tumor-associated macrophages (TAMs). Therefore, it is imperative to develop nanoparticles with high selectivity and precise targeting to enhance the efficacy of tumor treatment. In this study, we developed polyethylene glycol (PEG)- and aptamer (aptPD-L1)-functionalized silver nanotriangles (apt-PNTs) targeting PD-L1-overexpressing tumor cells and TAMs. Subsequently, we evaluated tumor-targeting ability, anti-tumor activity, and TAMs reprogramming effect through in vitro and in vivo studies. The study revealed that the synthesized nanoparticles exhibit exceptional photothermal properties and high stability. The apt-PNTs demonstrate selective uptake by TNBC cells and M2. In murine models, apt-PNTs accumulated maximally in tumors at 6 h. Under near-infrared laser irradiation (40-45 °C), apt-PNTs reduced M2 marker CD206 and increased M1 markers CD16/32 and iNOS, reprogramming TAMs and achieving 68.73 % tumor growth inhibition. In conclusion, in the absence of significant adverse reactions, apt-PNTs exhibit excellent photothermal properties and tumor-targeting ability. This work demonstrates the application of apt-PNTs-mediated PTT in promoting TAMs reprogramming and killing tumors, providing a potential approach for targeted therapy of TNBC.
Keywords: Photothermal therapy; Reprogramming; Triple-negative breast cancer; Tumor-associated macrophages; aptPD-L1.
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