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, t 1/2 = 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.

Multimodality Imaging of Silica and Silicon Materials In Vivo

“…and NIRF imaging (Ex λ = 465 nm, Em λ = 580 nm) was successfully used for confirming in vivo enhanced doxorubicin delivery into tumor. Even higher tumor uptakes were reported recently for biodegradable [ 89 Zr]bMSN‐PEG5k‐TRC105 particles in the same model . The bMSN particles were radiolabeled by using intrinsic radiolabeling via coordination of 89 Zr 4+ to the silanol groups of the porous silica framework, after which the particles were functionalized with PEG (5 kD) and the TRC105 antibody.…”

Mesoporous Silica and Organosilica Nanoparticles: Physical Chemistry, Biosafety, Delivery Strategies, and Biomedical Applications

“…The functionalization of mesoporous nanomaterials with radionuclides leads to higher selectivity and intensity of the PET signal than those of free radioisotopes . Several radioisotopes with different half‐lives ( t 1/2 ) were used to label MSNs for cancer theranostics, such as zirconium‐89 ( t 1/2 = 78.4 h), arsenic‐72 ( t 1/2 = 26.0 h), copper‐64 ( t 1/2 = 12.7 h), technetium‐99 m ( t 1/2 = 6.0 h), titanium‐45 ( t 1/2 = 3.08 h), fluorine‐18 ( t 1/2 = 109.8 min), and carbon‐11 ( t 1/2 = 20.4 min) …”

Radiolabeled inorganic nanoparticles for positron emission tomography imaging of cancer: an overview

“…76 The nanoparticles were PEGylated, conjugated with TRC105 and radiolabeled with 89 Zr via the chelator-free approach. In vivo PET imaging in 4T1 tumor bearing mice showed rapid tumor uptake which peaked to ~11.5 %ID/g at 4 h p.i., remaining constant afterwards up to 48 h p.i.…”