Laminin receptor specific therapeutic gold nanoparticles ( 198 AuNP-EGCg) show efficacy in treating prostate cancer
- 16 July 2012
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 109 (31), 12426-12431
- https://doi.org/10.1073/pnas.1121174109
Abstract
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.Keywords
This publication has 48 references indexed in Scilit:
- (−)-Gossypol Suppresses the Growth of Human Prostate Cancer Xenografts via Modulating VEGF Signaling–Mediated AngiogenesisMolecular Cancer Therapeutics, 2011
- Mouse Models of Prostate CancerProstate Cancer, 2011
- Molecular genetics of prostate cancer: new prospects for old challengesGenes & Development, 2010
- Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificityProceedings of the National Academy of Sciences, 2010
- Stereotactic body radiotherapy for organ-confined prostate cancerBMC Urology, 2010
- Green tea polyphenols for prostate cancer chemoprevention: A translational perspectivePhytomedicine, 2009
- Review: Green Tea Polyphenols in Chemoprevention of Prostate Cancer: Preclinical and Clinical StudiesNutrition and Cancer, 2009
- Screening and Prostate-Cancer Mortality in a Randomized European StudyNew England Journal of Medicine, 2009
- Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted miceBiomaterials, 2009
- Reduced-order constrained optimization in IMRT planningPhysics in Medicine & Biology, 2008