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

Abstract

Since the first use of biocompatible mesoporous silica (mSiO 2 ) nanoparticles as drug delivery vehicles, in vivo tumor targeted imaging and enhanced anti-cancer 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 64 Cu-labeling of uniform 80 nm sized mSiO 2 nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated that 64 Cu-NOTA-mSiO 2 -PEG-TRC105 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 tumorbearing 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. ASSOCIATED CONTENTSupporting Information: TEM images, FT-IR spectra, detailed characterization of mesoporous silica nanoparticles after each step of reaction, flow cytometry analysis, size exclusion column chromatography profile of the final conjugate, serum stability studies, serial PET images of 4T1 tumor-bearing mice after intravenous injection of 64 CuCl 2 , uptake in different tissues at serial time points postinjection in each group based on PET imaging, and DOX loading studies. This material is available free of charge via the Internet at

Focused Ultrasound‐Augmented Delivery of Biodegradable Multifunctional Nanoplatforms for Imaging‐Guided Brain Tumor Treatment

“…Among various inorganic nanosystems, biocompatible mesoporous silica nanoparticles (MSNs) have shown their high performance in molecular imaging,4 drug/gene/protein delivery,5 and biosensing 6. However, their biodegradability is one of the main biosafety issues hindering their further clinical translation.…”

Targeted drug delivery using genetically engineered diatom biosilica

“…However, simultaneous binding of drugs and antibodies to diatom silica particles has not been achieved and has hardly been investigated for synthetic mesoporous silica materials 15 . To date, there is only one successful example that has demonstrated the targeted delivery of doxorubicin to tumour-bearing tissue in mice using antibody-functionalized mesoporous silica nanoparticles 16 .…”

Nanoparticle Functionalization and Its Potentials for Molecular Imaging

“…NPs are conjugated with radiotracers for enhanced and prolonged PET imaging. Chen et al showed that Mesoporous Silica Particles (mSiO 2 ) linked with TRC105 antibody which is specific to CD105 present in the murine breast cancer cells, which are also functionalized with thiol and PEG molecules for its stability reduce opsonization 57. Now when the mSiO2 NPs are attached with 64 Cu radioisotope through the bond with NOTA (C 20 H 37 N 3 O 6 ) chemical molecule functionalized mSiO2 NPs by treating with 64 CuCl 2 , they become PET imaging agents as shown in Figure 5 .…”

“…Tumors were indicated by yellow arrowheads. Adapted with permission 57. Copyright 2013, American Chemical Society.…”