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.nanoradiotherapy | tumor metastases | localized therapy | polyphenols | cellular targeting R ecent data have confirmed that the incidence of prostate cancer is the highest among all estimated new cancer cases in American males, nearly double that of lung cancer (1). Globally, prostate cancer continues to be the second leading cause of cancer-related death in men (1). A detailed study involving 77,000 North Americans has shown that 10 y of regular prostate specific antigen (PSA) screening did not save a significant number of lives (2). Therefore, developments of new therapeutic protocols that provide effective control of the growth and propagation of prostate tumors have gained considerable clinical significance in the care and treatment of prostate cancer patients (3). The latest clinical trials on human prostate cancer patients using various experimental drugs further attest that shrinking prostate tumor sizes led to more than doubled survival in 70-80% of patients with aggressive cancers (3). Although a plethora of therapeutic approaches, which include utility of cytotoxic drugs (paclitaxel, estramustine, carboplatin, and doxorubicin) are currently in clinical practice, unfortunately, none of these chemotherapeutic agents offer a clinically efficient, affordable, and toxicologically safe regimen...
We report here an innovative feature of green nanotechnology-focused work showing that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango peels-serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. The laminin receptor specificity of mangiferin affords specific accumulation of therapeutic payloads of this new therapeutic agent within prostate tumors (PC-3) of human prostate tumor origin induced in mice which overexpress this receptor subtype. Detailed in vivo therapeutic efficacy studies, through the intratumoral delivery of MGF-AuNPs, show the retention of over 80% of the injected dose (ID) in prostate tumors up to 24 h. By three weeks post treatment, tumor volumes of the treated group of animals showed an over 5 fold reduction as compared to the control saline group. New opportunities for green nanotechnology and a new paradigm of using mangiferin as a tumor targeting agent in oncology for the application of MGF-AuNPs in the treatment of cancer are discussed.
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