Irradiation of tumors laden with gold nanoparticles (AuNP) results in radiation dose enhancement via increased secondary electron showers emanating from nanoparticle-radiation interactions. It is challenging to realize the true clinical potential of radiosensitization in vivo by non-invasively loading tumors with adequate amounts of gold. Preliminary data demonstrates that thermosensitive liposomes (TSLs) laden with AuNP accumulated within cancers via leaky vasculature, the enhanced permeability and retention (EPR) effect (Fig. iii - section G). Mild hyperthermia (42οC) induced by focused ultrasound (FUS) led to rupture of liposomes and deployment of gold payload deep within tumors. Subsequent irradiation generated significant delay of tumor-regrowth. Separately, we demonstrated that tumor specific targeted nanoparticles preferentially accumulate 5-fold more in tumors than pegylated nanoparticles (Fig. iv - section G). Subsequent irradiation of tumors containing gold caused significant delay of tumor-regrowth due to tumor-specific enhanced radiosensitization.