Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity

Nripen Chanda, Vijaya Kattumuri, Ravi Shukla, Ajit Zambre, Kavita Katti, Anandhi Upendran, Rajesh R. Kulkarni, Para Kan, Genevieve M. Fent, Stan W. Casteel, C. Jeffrey Smith, Evan Boote, J. David Robertson, Cathy Cutler, John R. Lever, Kattesh V. Katti, Raghuraman Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

Development of cancer receptor-specific gold nanoparticles will allow efficient targeting/optimum retention of engineered gold nanoparticles within tumors and thus provide synergistic advantages in oncology as it relates to molecular imaging and therapy. Bombesin (BBN) peptides have demonstrated high affinity toward gastrin-releasing peptide (GRP) receptors in vivo that are overexpressed in prostate, breast, and small-cell lung carcinoma. We have synthesized a library of GRP receptor-avid nanoplatforms by conjugating gold nanoparticles (AuNPs) with BBN peptides. Cellular interactions and binding affinities (IC50) of AuNP-BBN conjugates toward GRP receptors on human prostate cancer cells have been investigated in detail. In vivo studies using AuNP-BBN and its radiolabeled surrogate 198AuNP-BBN, exhibiting high binding affinity (IC50 in microgram ranges), provide unequivocal evidence that AuNP-BBN constructs are GRP-receptor-specific showing accumulationwith high selectivity in GRP-receptor-rich pancreatic acne in normal mice and also in tumors in prostate-tumor-bearing, severe combined immunodeficient mice. The i.p. mode of delivery has been found to be efficient as AuNP-BBN conjugates showed reduced RES organ uptake with concomitant increase in uptake at tumor targets. The selective uptake of this new generation of GRP-receptor-specific AuNP-BBN peptide analogs has demonstrated realistic clinical potential inmolecular imaging via x-ray computed tomography techniques as the contrast numbers in prostate tumor sites are severalfold higher as compared to the pretreatment group (Hounsfield unit = 150).

Original languageEnglish (US)
Pages (from-to)8760-8765
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number19
DOIs
StatePublished - May 11 2010
Externally publishedYes

Keywords

  • Bombesin
  • Computed tomography imaging
  • Gastrin-releasing peptide receptor
  • Gold nanoparticles
  • Prostate cancer

ASJC Scopus subject areas

  • General

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