Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity.
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).
Chanda
Nripen
N
Department of Radiology, Harry S. Truman Veterans Administration Medical Center, Columbia, MO, USA.
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
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
D018004:Receptors, Bombesin; D006046:Gold; D001839:Bombesin
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