Engineering Intrinsically Zirconium-89 Radiolabeled Self-Destructing Mesoporous Silica Nanostructures for In Vivo Biodistribution and Tumor Targeting Studies

Abstract

A systematic study of in vitro and in vivo behavior of biodegradable mesoporous silica nanoparticles (bMSNs), designed to carry multiple cargos (both small and macromolecular drugs) and subsequently self-destruct following release of their payloads, is presented. Complete degradation of bMSNs is seen within 21 d of incubation in simulated body fluid. The as-synthesized bMSNs are intrinsically radiolabeled with oxophilic zirconium-89 (89Zr, t1/2 = 78.4 h) radionuclide to track their in vivo pharmacokinetics via positron emission tomography imaging. Rapid and persistent CD105 specific tumor vasculature targeting is successfully demonstrated in murine model of metastatic breast cancer by using TRC105 (an anti-CD105 antibody)-conjugated bMSNs. This study serves to illustrate a simple, versatile, and readily tunable approach to potentially overcome the current challenges facing nanomedicine and further the goals of personalized nanotheranostics.