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


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 (IC(50)) 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 (198)AuNP-BBN, exhibiting high binding affinity (IC(50) in microgram ranges), provide unequivocal evidence that AuNP-BBN constructs are GRP-receptor-specific showing accumulation with 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 in molecular 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).

SUBMITTER: Chanda N 

PROVIDER: S-EPMC2889350 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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

Chanda Nripen N   Kattumuri Vijaya V   Shukla Ravi R   Zambre Ajit A   Katti Kavita K   Upendran Anandhi A   Kulkarni Rajesh R RR   Kan Para P   Fent Genevieve M GM   Casteel Stan W SW   Smith C Jeffrey CJ   Boote Evan E   Robertson J David JD   Cutler Cathy C   Lever John R JR   Katti Kattesh V KV   Kannan Raghuraman R  

Proceedings of the National Academy of Sciences of the United States of America 20100421 19


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 nanopl  ...[more]

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