Journal
ACS NANO
Volume 7, Issue 10, Pages 9027-9039Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn403617J
Keywords
mesoporous silica (mSiO(2)) nanoparticles; tumor angiogenesis; in vivo tumor targeting; positron emission tomography (PET); drug delivery; theranostics
Categories
Funding
- University of Wisconsin-Madison
- National Institutes of Health [NIBIB/NCI 1R01CA169365]
- Department of Defense [W81XWH-11-1-0644]
- American Cancer Society [125246-RSG-13-099-01-CCE]
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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.
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