2007 NSTI Nanotechnology Conference and Trade Show - Nanotech 2007 - 10th Annual

Prostate-tumor Specific Gold Nanoparticles for Imaging and Therapy

V. Kattumuri, R. Kannan, G. Fent, S. Casteel, D. Lubahn, D. Robertson, G. Sieckmann, C. Cutler and K.V. Katti
University of Missouri - Columbia, US

Keywords:
Gold Nanoparticles, Bombesin, Cancer

Abstract:
The potential application of gold nanoparticles (AuNPs) to enhance contrast in CT imaging for early cancer detection, and subsequently to enhance the effectiveness of cancer treatment regimen, has given tremendous impetus to the design and development of cancer specific gold nanoparticles. In the present work, prostate tumor specific AuNPs were synthesized by conjugating AuNPs with bombesin peptide. Bombesin (BBN) has shown high affinity towards Gastrin Releasing Peptide (GRP) receptors that are over-expressed in prostate cancer. AuNPs stabilized with exchangable starch molecules and thioctic acid-BBN (SSBBN) are used as precursors. Thioctic acid contains disulfide (S-S) moiety, which oxidatively adds to gold nanoparticles to form the conjugate. The number of SSBBN coated over AuNP was varied by treating AuNPs with varying concentrations of SSBBN. The AuNP-SSBBN conjugates were evaluated for their in vitro binding affinity (IC50) towards PC-3 prostate cancer cell line. The IC-50 values reveal that these bioconjugates show excellent in vitro specificity. Biodistribution studies of AuNP-SSBBN were performed in normal mice. Significant accumulation in pancreas indicates that these conjugates specifically target GRP receptors. TRAMP mice models were used for prostate-tumor affinity studies. In TRAMP mice, which are classic prostate cancer models, AuNP-SSBBN conjugates exhibit significant accumulation in prostate tumor. These results show that AuNP-SSBBN conjugates demonstrate excellent in vivo specificity towards prostate cancer. The accumulation of AuNP-BBN conjugates in prostate tumor site may be utilized to enhance contrast in the CT imaging for early detection of prostate cancer. Likewise, AuNP-SSBBN conjugates at tumor sites can be explored for use in radiotherapy and photothermal therapy of prostate cancer.

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