Radioactive gold nanoparticles in cancer therapy: therapeutic efficacy studies of GA-198AuNP nanoconstruct in prostate tumor-bearing mice.
Biocompatibility studies and cancer therapeutic applications of nanoparticulate beta-emitting gold-198 (198Au; beta(max) = 0.96 MeV; half-life of 2.7 days) are described. Gum arabic glycoprotein (GA)-functionalized gold nanoparticles (AuNPs) possess optimum sizes (12-18 nm core diameter and 85 nm hydrodynamic diameter) to target individual tumor cells and penetrate through tumor vasculature and pores. We report the results of detailed in vivo therapeutic investigations demonstrating the high tumor affinity of GA-198AuNPs in severely compromised immunodeficient (SCID) mice bearing human prostate tumor xenografts. Intratumoral administration of a single dose of beta-emitting GA-198AuNPs (70 Gy) resulted in clinically significant tumor regression and effective control in the growth of prostate tumors over 30 days. Three weeks after administration of GA-198AuNPs, tumor volumes for the treated animals were 82% smaller as compared with tumor volume of control group. The treatment group showed only transitory weight loss in sharp contrast to the tumor-bearing control group, which underwent substantial weight loss. Pharmacokinetic studies have provided unequivocal evidence for the optimum retention of therapeutic payload of GA-198AuNPs within the tumor site throughout the treatment regimen with minimal or no leakage of radioactivity to various nontarget organs. The measurements of white and red blood cells, platelets, and lymphocytes within the treatment group resembled those of the normal SCID mice, thus providing further evidence on the therapeutic efficacy and concomitant in vivo tolerance and nontoxic features of GA-198AuNPs.


BACKGROUND
In this study, the biocompatibility and cancer therapeutic applications of glycoprotein (GA) functionalized gold nanoparticles containing b-emitting Au-198 are described in SCID mice bearing human prostate tumor xenografts. The findings of significant therapeutic efficacy, good in vivo tolerance and non-toxic features make these particles ideal candidates for future human applications.
Chanda
Nripen
N
Department of Radiology, University of Missouri, Columbia, Missouri 65211, USA.
Kan
Para
P
Watkinson
Lisa D
LD
Shukla
Ravi
R
Zambre
Ajit
A
Carmack
Terry L
TL
Engelbrecht
Hendrik
H
Lever
John R
JR
Katti
Kavita
K
Fent
Genevieve M
GM
Casteel
Stan W
SW
Smith
C Jeffrey
CJ
Miller
William H
WH
Jurisson
Silvia
S
Boote
Evan
E
Robertson
J David
JD
Cutler
Cathy
C
Dobrovolskaia
Marina
M
Kannan
Raghuraman
R
Katti
Kattesh V
KV
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006023:Glycoproteins / Q000737:chemistry*; D006050:Gold Radioisotopes / Q000737:chemistry* / Q000627:therapeutic use*; D006170:Gum Arabic / Q000737:chemistry*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000627:therapeutic use; D016896:Treatment Outcome
D004337:Drug Carriers; D006023:Glycoproteins; D006050:Gold Radioisotopes; D019275:Radiopharmaceuticals; D006170:Gum Arabic