In vivo tumor targeting and image-guided drug delivery with antibody-conjugated, radiolabeled mesoporous silica nanoparticles

Feng Chen, Hao Hong, Yin Zhang, Hector F. Valdovinos, Sixiang Shi, Glen S. Kwon, Charles P. Theuer, Todd E. Barnhart, Weibo Cai

Research output: Journal article publicationJournal articleAcademic researchpeer-review

265 Citations (Scopus)

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 languageEnglish
Pages (from-to)9027-9039
Number of pages13
JournalACS Nano
Volume7
Issue number10
Early online date1 Oct 2013
DOIs
Publication statusPublished - 22 Oct 2013
Externally publishedYes

Keywords

  • drug delivery
  • in vivo tumor targeting
  • mesoporous silica (mSiO) nanoparticles
  • positron emission tomography (PET)
  • theranostics
  • tumor angiogenesis

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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