Integrin αvβ3-targeted gold nanoshells augment tumor vasculature-specific imaging and therapy.

Huan Xie, Parmeswaran Diagaradjane, Amit A. Deorukhkar, Beth Goins, Ande Bao, William T. Phillips, Zheng Wang, Jon Schwartz, Sunil Krishnan

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Gold nanoshells (NSs) have already shown great promise as photothermal actuators for cancer therapy. Integrin αvβ3 is a marker that is specifically and preferentially overexpressed on multiple tumor types and on angiogenic tumor neovasculature. Active targeting of NSs to integrin αvβ3 offers the potential to increase accumulation preferentially in tumors and thereby enhance therapy efficacy. Enzyme-linked immunosorbent assay (ELISA) and cell binding assay were used to study the in vitro binding affinities of the targeted nanoconjugate NS-RGDfK. In vivo biodistribution and tumor specificity were analyzed using 64Cu-radiolabeled untargeted and targeted NSs in live nude rats bearing head and neck squamous cell carcinoma (HNSCC) xenografts. The potential thermal therapy applications of NS-RGDfK were evaluated by subablative thermal therapy of tumor xenografts using untargeted and targeted NSs. ELISA and cell binding assay confirmed the binding affinity of NS-RGDfK to integrin αvβ3. Positron emission tomography/computed tomography imaging suggested that tumor targeting is improved by conjugation of NSs to cyclo(RGDfK) and peaks at ~20 hours postinjection. In the subablative thermal therapy study, greater biological effectiveness of targeted NSs was implied by the greater degree of tumor necrosis. The results presented in this paper set the stage for the advancement of integrin αvβ3-targeted NSs as therapeutic nanoconstructs for effective cancer therapy.

Original languageEnglish (US)
Pages (from-to)259-269
Number of pages11
JournalInternational journal of nanomedicine
Volume6
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

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