In Vivo Tumor Targeting and Image-Guided Drug Delivery with Antibody-Conjugated, Radio labeled Mesoporous Silica Nanoparticles

Since the first use of biocompatible mesoporous silica (mSiO(2)) nanoparticles as drug delivery vehicles, in vivo tumor targeted imaging and enhanced anticancer drug delivery has remained a major challenge. In this work, we describe the development of functionalized mSiO(2) nanoparticles for actively targeted positron emission tomography (PET) imaging and drug delivery in 4T1 murine breast tumor-bearing mice. Our structural design involves the synthesis, surface functionalization with thiol groups, PEGylation, TRC105 antibody (specific for CD105/endoglin) conjugation, and Cu-64-labeling of uniform 80 nm sized mSiO(2) nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated that Cu-64-NOTA-mSiO(2)-PEG-TRC10S could accumulate prominently at the 4T1 tumor site via both the enhanced permeability and retention effect and TRC105-mediated binding to tumor vasculature CD105. As a proof-of-concept, we also demonstrated successful enhanced tumor targeted delivery of doxorubicin (DOX) in 4T1 tumor-bearing mice after intravenous injection of DOX-loaded NOTA-mSiO(2)-PEG-TRC105, which holds great potential for future image-guided drug delivery and targeted cancer therapy.