Ultrasmall Porous Silica Nanoparticles With Enhanced Pharmacokinetics For Cancer Theranostics

Theranostic nanoparticles hold the potential to greatly improve cancer management by providing personalized medicine. Although many theranostic nanoconstructs have been successful in preclinical studies, clinical translation is still hampered by their limited targeting capability and lack of successful therapeutic efficacy. We report the use of novel ultrasmall porous silica nanoparticles (UPSN) with enhanced in vivo pharmacokinetics such as high target tissue accumulation (12% ID/g in the tumor) and evasion from the reticuloendothelial system (RES) organs. Herein, UPSN is conjugated with the isotopic pair Y-90/86, enabling both noninvasive imaging as well as internal radiotherapy. In vivo PET imaging demonstrates prolonged blood circulation and excellent tumor contrast with Y-86-DOTA-UPSN. Tumor-to-muscle and tumor-to-liver uptake values were significantly high (12.4 +/- 1.7 and 1.5 +/- 0.5, respectively), unprecedented for inorganic nanomaterials. Y-90-DOTA-UPSN significantly inhibits tumor growth and increases overall survival, indicating the promise of UPSN for future clinical translation as a cancer theranostic agent.