DOI: 10.1073/pnas.1002143107. Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity

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

10.1073/pnas.1002143107

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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).

Bibliography

Chanda, N., Kattumuri, V., Shukla, R., Zambre, A., Katti, K., Upendran, A., Kulkarni, R. R., Kan, P., Fent, G. M., Casteel, S. W., Smith, C. J., Boote, E., Robertson, J. D., Cutler, C., Lever, J. R., Katti, K. V., & Kannan, R. (2010). Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity. Proceedings of the National Academy of Sciences, 107(19), 8760â8765.

Authors 17

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

References 34 Referenced 270

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DJM Gallant, C Mercier, A Guilbot, Electron microscopy of starch granules modified by bacterial a-amylase. Cereal Chem 49, 354–365 (1972). / Cereal Chem / Electron microscopy of starch granules modified by bacterial a-amylase by Gallant DJM (1972)
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J Schuhmacher, et al., GRP receptor-targeted PET of a rat pancreas carcinoma xenograft in nude mice with a 68Ga-labeled bombesin(6-14) analog. J Nucl Med 46, 691–699 (2005). / J Nucl Med / GRP receptor-targeted PET of a rat pancreas carcinoma xenograft in nude mice with a 68Ga-labeled bombesin(6-14) analog by Schuhmacher J (2005)
10.1038/labinvest.3700404
CJ Smith, et al., Radiochemical investigations of gastrin-releasing peptide receptor-specific [(99m)Tc(X)(CO)3-Dpr-Ser-Ser-Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH2)] in PC-3, tumor-bearing, rodent models: Syntheses, radiolabeling, and in vitro/in vivo studies where Dpr = 2,3-diaminopropionic acid and X = H2O or P(CH2OH)3. Cancer Res 63, 4082–4088 (2003). / Cancer Res / Radiochemical investigations of gastrin-releasing peptide receptor-specific [(99m)Tc(X)(CO)3-Dpr-Ser-Ser-Ser-Gln-Trp-Ala-Val-Gly-His-Leu-Met-(NH2)] in PC-3, tumor-bearing, rodent models: Syntheses, radiolabeling, and in vitro/in vivo studies where Dpr = 2,3-diaminopropionic acid and X = H2O or P(CH2OH)3 by Smith CJ (2003)
10.1021/bc060400x
10.1016/S0969-8051(02)00391-8
10.1016/j.biomaterials.2008.12.038

Dates

Type	When
Created	15 years, 4 months ago (April 21, 2010, 10:47 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:39 p.m.)
Indexed	17 minutes ago (Aug. 27, 2025, 12:12 p.m.)
Issued	15 years, 4 months ago (April 21, 2010)
Published	15 years, 4 months ago (April 21, 2010)
Published Online	15 years, 4 months ago (April 21, 2010)
Published Print	15 years, 3 months ago (May 11, 2010)

Funders 0

None

BibTeX

@article{Chanda_2010, title={Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity}, volume={107}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1002143107}, DOI={10.1073/pnas.1002143107}, number={19}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chanda, Nripen and Kattumuri, Vijaya and Shukla, Ravi and Zambre, Ajit and Katti, Kavita and Upendran, Anandhi and Kulkarni, Rajesh R. and Kan, Para and Fent, Genevieve M. and Casteel, Stan W. and Smith, C. Jeffrey and Boote, Evan and Robertson, J. David and Cutler, Cathy and Lever, John R. and Katti, Kattesh V. and Kannan, Raghuraman}, year={2010}, month=apr, pages={8760–8765} }

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