Notably, when RRM2 was overexpressed in tumor cells andHVECs, tumor growth was significantly accelerated, and the therapeuticeffects of P-Fe3O4@Pal@HM and NIR were suppressed.These findings highlight the effectiveness of P-Fe3O4@Pal@HM combined with NIR for treating osteosarcoma by directlytargeting and killing tumor cells and endothelial cells through mitochondrialapoptosis and inhibition of DNA repair while simultaneously inducingmacrophage polarization to achieve synergistic tumor cell destruction. Here, RRM2 is linked to neoplasm.