title: 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).
authors.affiliation: Department of Radiology, Harry S. Truman Veterans Administration Medical Center, Columbia, MO, USA.
authors.forename: Nripen
authors.initials: N
authors.lastname: Chanda
authors.forename: Vijaya
authors.initials: V
authors.lastname: Kattumuri
authors.forename: Ravi
authors.initials: R
authors.lastname: Shukla
authors.forename: Ajit
authors.initials: A
authors.lastname: Zambre
authors.forename: Kavita
authors.initials: K
authors.lastname: Katti
authors.forename: Anandhi
authors.initials: A
authors.lastname: Upendran
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Kulkarni
authors.forename: Para
authors.initials: P
authors.lastname: Kan
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Fent
authors.forename: Stan W
authors.initials: SW
authors.lastname: Casteel
authors.forename: C Jeffrey
authors.initials: CJ
authors.lastname: Smith
authors.forename: Evan
authors.initials: E
authors.lastname: Boote
authors.forename: J David
authors.initials: JD
authors.lastname: Robertson
authors.forename: Cathy
authors.initials: C
authors.lastname: Cutler
authors.forename: John R
authors.initials: JR
authors.lastname: Lever
authors.forename: Kattesh V
authors.initials: KV
authors.lastname: Katti
authors.forename: Raghuraman
authors.initials: R
authors.lastname: Kannan
mesh_terms: D000818:Animals; D001839:Bombesin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006046:Gold / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D008970:Molecular Weight; D009369:Neoplasms / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000378:metabolism*; D012995:Solubility / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
chemical_list: D018004:Receptors, Bombesin; D006046:Gold; D001839:Bombesin
references.citation: N Engl J Med. 2009 Mar 26;360(13):1310-9
references.pmid: 19297565
references.citation: Ann Urol (Paris). 2004 Oct;38(5):207-24
references.pmid: 15570705
references.citation: Nanomedicine. 2010 Apr;6(2):201-9
references.pmid: 19914401
references.citation: Nano Lett. 2009 May;9(5):1798-805
references.pmid: 19351145
references.citation: Radiology. 1981 Sep;140(3):751-61
references.pmid: 7280246
references.citation: Mol Ther. 2009 Jan;17(1):162-8
references.pmid: 18827803
references.citation: Eur J Nucl Med Mol Imaging. 2003 Oct;30(10):1378-82
references.pmid: 12920485
references.citation: Cancer Res. 2008 Mar 15;68(6):1970-8
references.pmid: 18339879
references.citation: Pharm Res. 1992 Dec;9(12):1534-9
references.pmid: 1488394
references.citation: Br J Radiol. 2006 Mar;79(939):248-53
references.pmid: 16498039
references.citation: Bioconjug Chem. 2007 Sep-Oct;18(5):1516-20
references.pmid: 17760415
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17356-61
references.pmid: 18978032
references.citation: Nat Rev Urol. 2009 Apr;6(4):191-203
references.pmid: 19352394
references.citation: Part Fibre Toxicol. 2007 Oct 19;4:10
references.pmid: 17949501
references.citation: Biomaterials. 2009 Apr;30(10):1928-36
references.pmid: 19131103
references.citation: Nano Lett. 2008 Dec;8(12):4593-6
references.pmid: 19367807
references.citation: Top Magn Reson Imaging. 1995 Winter;7(1):54-68
references.pmid: 7532980
references.citation: J Am Chem Soc. 2006 Sep 6;128(35):11342-3
references.pmid: 16939243
references.citation: Nat Nanotechnol. 2007 Dec;2(12):751-60
references.pmid: 18654426
references.citation: Nucl Med Biol. 2003 Feb;30(2):101-9
references.pmid: 12623108
references.citation: Tumori. 2002 May-Jun;88(3):S28-30
references.pmid: 12365378
references.citation: J Nucl Med. 2005 Apr;46(4):691-9
references.pmid: 15809493
references.citation: Lab Invest. 2006 May;86(5):517-25
references.pmid: 16568109
references.citation: Cancer Res. 2009 Aug 1;69(15):6184-91
references.pmid: 19643734
references.citation: ACS Nano. 2009 Oct 27;3(10):2941-52
references.pmid: 19856978
references.citation: Prostate. 1994 Jul;25(1):29-38
references.pmid: 8022709
references.citation: Small. 2007 Feb;3(2):333-41
references.pmid: 17262759
references.citation: Cancer Res. 2003 Jul 15;63(14):4082-8
references.pmid: 12874010
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18437-42
references.pmid: 19841273
references.citation: Acc Chem Res. 2008 Dec;41(12):1578-86
references.pmid: 18447366
references.citation: Annu Rev Med. 2008;59:251-65
references.pmid: 17937588