Bombesin functionalized gold nanoparticles show cancer receptor specificity: Implications in molecular imaging and therapy

Chanda, N, Kattumuri, V, Shukla, R, Zambre, A, Katti, K, Upendran, A, Kulkarni, R, Kan, P, Fent, G, Casteel, S, Smith, C, Boote, E, Cutler, C, Lever, J, Robertson, J, Katti, K and Kannan, R 2010, 'Bombesin functionalized gold nanoparticles show cancer receptor specificity: Implications in molecular imaging and therapy', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 19, pp. 8760-8765.


Document type: Journal Article
Collection: Journal Articles

Title Bombesin functionalized gold nanoparticles show cancer receptor specificity: Implications in molecular imaging and therapy
Author(s) Chanda, N
Kattumuri, V
Shukla, R
Zambre, A
Katti, K
Upendran, A
Kulkarni, R
Kan, P
Fent, G
Casteel, S
Smith, C
Boote, E
Cutler, C
Lever, J
Robertson, J
Katti, K
Kannan, R
Year 2010
Journal name Proceedings of the National Academy of Sciences of the United States of America
Volume number 107
Issue number 19
Start page 8760
End page 8765
Total pages 6
Publisher National Academy of Sciences
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 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).
Subject Nanomedicine
Cancer Cell Biology
Nanomaterials
Keyword(s) Gold nanoparticles
bombesin
gastrin-releasing peptide receptor
prostate cancer
computed tomography imaging
DOI - identifier 10.1073/pnas.1002143107
Copyright notice © 2010 National Academy of Sciences
ISSN 0027-8424
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