“Radioactive Gold-198 Nanoparticles In Nanomedicine: Green Nanotechnologies in Digital and Molecular Agents for Innovative Cancer Diagnosis and Therapy Approaches in Oncology“
Cancer alone continues to kill more people than AIDS, malaria, and tuberculosis combined. According to the International Agency for Research on Cancer, there were 12.7 million new cancer cases in 2008. The World Health Organization projects that without major breakthroughs in cancer prevention, discovery of new and accurate diagnostic modalities and development of highly effective therapeutic approaches, the global number of deaths from cancer will increase by nearly 80% by 2030, with most occurring in low- and middle-income countries. There are over 100 pharmaceutical formulations approved by the US Food and Drug Administration (FDA) in order to combat this deadly pandemic. Although surgery and radiation treatments are the initial treatments for most cancers, a large number of oncological approaches are being used to control or cure cancer. Today cancer patients have more choices in which treatment or combination of treatments may be used encompassing three areas of emphasis: (a) Chemotherapy, (b) Hormone therapy; (c) Biological treatment. Despite the currently available choice of established anticancer agents for first-line of activity against cancer, effective delivery of chemotherapeutic, hormonal and biological pharmaceuticals to the tumor tissue and cancer cells selectively continues to be the most vexing problems in cancer oncology. Problems associated with effective delivery of cancer drugs pose severe oncological challenges especially when treating solid tumors (sarcomas, carcinomas, and lymphomas) which account for over 85% of all human cancers. Circumventing these problems is not easy because molecular and cellular biology of neoplastic cells alone has failed to explain the non-uniform uptake of these agents in solid tumors. Repeated delivery of cancer drugs leads to systemic toxicity creating major collateral adverse effects where cancer cells mutate making them resistant to chemotherapeutic treatments. Therefore, the discovery of new drug delivery approaches that effectively penetrate extracellular compartments consisting of vascular and interstitial valves within solid tumors is of profound importance.
Radioactive nanoparticles with diagnostic and therapeutic capabilities provide intelligent drug delivery systems to maximize therapeutic activity and to minimize undesirable side-effects. For example the radioisotope of gold metal, Au-198, provides a desirable beta energy emission and half-life that destroys tumor cells/tumor tissue (βmax = 0.96 MeV; half-life of 2.7 days). Its penetration range (up to 4 mm in tissue or up to 1100 cell diameters) is sufficiently long to provide cross-fire effects to destroy tumor cells/tissue, but short enough to minimize radiation exposure to adjacent tissues. One particularly attractive feature of radioactive gold nanoparticles is that it does not have to be incorporated into every tumor cell to have a therapeutic effect. The path length of the emitted radiation is sufficient to allow effective therapy following uptake into a subpopulation of tumor cells. It is this feature that has attracted recent attention to apply nanotechnology for the effective delivery of therapeutic doses of beta emitting nanoparticles selectively to tumor tissue and tumor cells. We have reported the synthesis of novel radioactive gold nanoparticles using the trimeric phosphine (referred to as ‘Katti Peptide’ discovered in our laboratory (1). In our continued efforts to apply Green Nanotechnology for the development of therapeutic radioactive gold nanoparticles, recently we have discovered that the high antioxidant capacity of Epigallocatechin gallate (EGCG) , which is the most abundant catechin polyphenol in tea, can be used to convert radioactive Gold-198 precursor to the corresponding biocompatible radioactive gold nanoparticles functionalized with Laminin receptor specific EGCG (2). Most recently, we have shown that mangiferin—a glucose functionalized xanthanoid, 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 (3). Interaction of mangiferin with Au-198 gold precursor affords MGF-198AuNPs as the beta emissions of Au-198 provides unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. 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-198AuNPs, shows retention of over 80% of the injected dose (ID) in prostate tumors up to 24 h. This lecture will provide: (a) scope and prospects of beta emitting radioisotopes in nanomedicine; (b) details on the intervention of nuclear activation analysis and various radioanalytical approaches for the production of tumor specific radioactive gold-198 nanoparticles; and (c) full in vivo investigations on therapeutic properties of MGF-198-AuNP agent in treating prostate tumors and (d) the overall implications of Green Nanotechnology of therapeutic beta emitting nanoparticles in oncology.
Prof. Kattesh V. Katti, Globally recognized as the ‘Father of Green Nanotechnology’, Professor Kattesh V. Katti, MSc Ed, PhD, DSc, FRSC, FNAI, Curators’ Professor of Radiology, Director, Institute of Green Nanotechnology, within the Medical School, University of Missouri, Columbia, USA—is internationally renowned as a leader in the interconnecting fields of—chemistry, radiopharmaceutical sciences, nanotechnology/green nanotechnology and nanomedicine—for biomedical applications, specifically for molecular imaging and therapy of living subjects. Dr. Katti is considered to be a pioneer in the field of Nano-Ayurvedic Medicine—a new medical modality which he has discovered by the application of Green Nanotechnology to Ayurvedic-Holistic Medicine. The US Patents and Trade Marks office has approved the use of ‘Nano-Ayurvedic Medicine’ name in the products of this new medical modality. For the ground breaking discoveries in medicine, Dr. Katti has been awarded a number of international awards and citations, which include: 2018 Professor of the European Union in Green Nanotechnology; 2018 WHOs WHO Marquis “Albert Nelson Marquis Lifetime Achievement Award”; 2017 Distinguished Alumni Award from the University of Missouri for his life time achievements; Winner of the 2016 ‘Person of the Year in Science’ award. Dr. Katti was selected for this coveted award for his pioneering research in Green Nanotechnology with applications to Nanomedicine. Dr. Katti has won the International Hevesy Medal Award (2015)—A Global award for excellence in Nuclear Sciences and Nuclear Medicine—considered equivalent to a Nobel Prize in Nuclear Sciences; Elected to the fellowship of the National Academy of Inventors (2015) recognizing the discovery of ‘Katti Peptides’—a group of peptides used in biomedical sciences and nanomedicine research. In recognitions of his ground breaking discoveries of radioactive gold nanoparticles in cancer therapy with implications in theranostics and plethora of original research in SPECT imaging, Dr. Katti has been recognized as One of the ‘25 Most Influential Scientists In Molecular Imaging in the World’ by RT Image. Dr. Katti has received the ‘Father of Green Nanotechnology’ citation by the Nobel Prize Winner Norman Borlaug, and has been bestowed with the Gauss Professorship—Hall of Fame—from the Gottingen Academy of Sciences. Dr. Katti is the first immigrant American to win the ‘Outstanding Missourian Award’—the highest civilian award from the Governor of the State of Missouri; former awardees of this highly coveted award include Walter Elias “Walt” Disney, Mark Twain, and Walter Cronkite…Dr. Katti has won the ‘Outstanding Scientists Fellows’ award and inducted as a Fellow of the St Louis Academy of Science—one of the oldest scientific academies of the world and many more. In 2013, Dr. Katti was elected as a fellow of the American Association for the Advancement of Science with a citation “for distinguished contributions encompassing nanoscale chemistry, particularly for ground breaking discoveries enabling application of nanotechnology concepts for biomedical applications”. His unprecedented discoveries of the production of tumor specific gold nanoparticles through 100% green processes have been cited as the Editor’s choice in Nature, Future Medicine, in Science (AAAS), in Popular Science, and by the Discovery Channel.