Anticancer effects of DNA-functionalized gold Nanoparticle-Mediated photothermal therapy

Vascular endothelial growth factor (VEGF)-targeted therapies are promising in inhibiting tumor angiogenesis but often face limitations due to resistance and incomplete efficacy. Combining VEGF inhibition with photothermal therapy (PTT), which uses nanoparticles such as gold nanoparticles to generate heat upon light exposure, offers a potential solution by targeting both the tumor vasculature and the tumor cells directly. However, the molecular mechanisms driving the synergy between these treatments remain unclear. In this study we employed quantitative proteomics to investigate the molecular alterations induced by combining VEGF-targeted aptamers with PTT in MCF-7 breast cancer cells. Our proteomic analysis revealed significant changes in proteins involved in cell cycle regulation, RNA splicing, and stress responses, particularly those associated with p53 activation and endoplasmic reticulum stress. Specifically, the combined treatment suppressed cell cycle progression, activated endoplasmic reticulum stress, and inhibited stress granule disassembly, leading to increased tumor cell death. These findings provide new insights into the therapeutic mechanisms of this combination therapy and also demonstrate the general potential of quantitative proteomics in elucidating complex treatment effects. Furthermore, this study highlights how proteomics can help identify biomarkers for treatment efficacy and guide the optimization of combination therapies for cancer.