Albumin-Templated Manganese Dioxide Nanoparticles for Enhanced Radioisotope Therapy

Although nanoparticle-based drug delivery systems have been widely explored for tumor-targeted delivery of radioisotope therapy (RIT), the hypoxia zones of tumors on one hand can hardly be reached by nanoparticles with relatively large sizes due to their limited intratumoral diffusion ability, on the other hand often exhibit hypoxia-associated resistance to radiation-induced cell damage. To improve RIT treatment of solid tumors, herein, radionuclide ¹³¹ I labeled human serum albumin (HSA)-bound manganese dioxide nanoparticles (¹³¹ I-HSA-MnO₂ ) are developed as a novel RIT nanomedicine platform that is responsive to the tumor microenvironment (TME). Such ¹³¹ I-HSA-MnO₂ nanoparticles with suitable sizes during blood circulation show rather efficient tumor passive uptake owing to the enhanced permeability and retention effect, as well as little retention in other normal organs to minimize radiotoxicity. The acidic TME can trigger gradual degradation of MnO₂ and thus decomposition of ¹³¹ I-HSA-MnO₂ nanoparticles into individual ¹³¹ I-HSA with sub-10 nm sizes and greatly improves intratumoral diffusion. Furthermore, oxygen produced by MnO₂ -triggered decomposition of tumor endogenous H₂ O₂ would be helpful to relieve hypoxia-associated RIT resistant for those tumors. As the results, the ¹³¹ I-HSA-MnO₂ nanoparticles appear to be a highly effective RIT agent showing great efficacy in tumor treatment upon systemic administration.