Abstract
Since the first use of biocompatible mesoporous silica (mSiO2) 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 mSiO2 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 64Cu-labeling of uniform 80 nm sized mSiO2 nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated that 64Cu-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 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.
Original language | English |
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Pages (from-to) | 9027-9039 |
Number of pages | 13 |
Journal | ACS Nano |
Volume | 7 |
Issue number | 10 |
Early online date | 1 Oct 2013 |
DOIs | |
Publication status | Published - 22 Oct 2013 |
Externally published | Yes |
Keywords
- drug delivery
- in vivo tumor targeting
- mesoporous silica (mSiO) nanoparticles
- positron emission tomography (PET)
- theranostics
- tumor angiogenesis
ASJC Scopus subject areas
- General Materials Science
- General Engineering
- General Physics and Astronomy