Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer.
Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the (198)Au β-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible (198)AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of (198)AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable (198)AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.
Department of Radiology, Harry S Truman Veterans Administration Medical Center, and Missouri University Research Reactor, University of Missouri, Columbia, MO 65212, USA.
Ravi
R
Shukla
Nripen
N
Chanda
Ajit
A
Zambre
Anandhi
A
Upendran
Kavita
K
Katti
Rajesh R
RR
Kulkarni
Satish Kumar
SK
Nune
Stan W
SW
Casteel
Charles Jeffrey
CJ
Smith
Jatin
J
Vimal
Evan
E
Boote
J David
JD
Robertson
Para
P
Kan
Hendrik
H
Engelbrecht
Lisa D
LD
Watkinson
Terry L
TL
Carmack
John R
JR
Lever
Cathy S
CS
Cutler
Charles
C
Caldwell
Raghuraman
R
Kannan
Kattesh V
KV
Katti
D000818:Animals; D016588:Anticarcinogenic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D006046:Gold / Q000493:pharmacokinetics* / Q000494:pharmacology; D006050:Gold Radioisotopes / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D016513:Mice, SCID; D010316:Particle Size; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D016588:Anticarcinogenic Agents; D006050:Gold Radioisotopes; D006046:Gold; D002392:Catechin; C045651:epigallocatechin gallate