The limited
tumor specific uptake of nanoparticles is one of major bottlenecks for clinical translation of nanoscale
therapeutics. Herein, we propose a strategy using internal
radioisotope therapy (RIT) delivered by liposomal nanoparticles to improve the
tumor vasculature permeability, so as to increase the
tumor specific uptake of the second-wave therapeutic nanoparticles for enhanced
cancer therapies. Via a convenient method, a therapeutic
radioisotope iodine-131 is labeled onto
albumin-encapsulated
liposomes with greatly improved radiolabeling stability compared to 131I labeled
albumin. The obtained 131I-liposome with long blood half-life could accumulate in the
tumor and damage
tumor blood endothelial cells to improve the
tumor vascular permeability. As the result, the
tumor retention of the second wave of liposomal nanoparticles could be greatly increased owing to the RIT-enhanced EPR effect. In three separated experiments, we then demonstrate that such strategy could be utilized for
photothermal therapy (PTT),
hypoxia-activated
chemotherapy (HCT) and checkpoint blockade
immunotherapy, all of which could be enhanced by RIT with excellent in vivo synergistic therapeutic outcomes. Our work highlights the great promises of employing nanoparticle-mediated RIT to modulate
tumor vasculature for further enhanced
cancer therapy, and may have potential value for clinical translation.