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 198Au 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 198AuNPs 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 198AuNP-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 198AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.
Written by:
Shukla R, Chanda N, Zambre A, Upendran A, Katti K, Kulkarni RR, Nune SK, Casteel SW, Smith CJ, Vimal J, Boote E, Robertson JD, Kan P, Engelbrecht H, Watkinson LD, Carmack TL, Lever JR, Cutler CS, Caldwell C, Kannan R, Katti KV. Are you the author?
Departments of Radiology and Physics, Nuclear Science and Engineering Institute, Chemistry, Veterinary Pathobiology, Medical Pharmacology and Physiology, Pathology and Anatomical Science, Ellis Fischel Cancer Center, Harry S. Truman Veterans Administration Medical Center, and Missouri University Research Reactor, University of Missouri, Columbia, MO 65212.
Reference: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12426-31.
doi: 10.1073/pnas.1121174109
PubMed Abstract
PMID: 22802668
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