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Velaphi C Thipe,1 Nya Hall,1 Amoolya Pandurangi,2 Samuel Ajayi,3 Prosper Emeh,3 Iti Gauttam,3 Rania Ghamgui,3 Fatima Hameedat,3 Sihem Khelil,3 Nhu Ky Ly,3 Mahmoud Salim,3 Anum Shahid Waleed,3 Prajna Hegde,4 Vrushali Hegde,4 Deepa Prakash,4 Ilaadevi Hegde,4 Kavita Katti,1 Alice Raphael Karikachery,1 Emilie Roger,3,5 Anne Landreau,3,6 Kattesh V Katti1,7,8 1Department of Radiology, University of Missouri, Columbia, MO, 65212, USA; 2Department of Biology, Saint Louis University, St. Louis, MO, 63103, USA; 3Pharmacy School, UNIV Angers, Angers, F-49000, France; 4Kadamba Intrac Private Ltd, Bangalore, KA, 560011, India; 5MINT, INSERM 1066, CNRS 6021, University of Angers, Angers, France; 6Univ Angers, Univ Brest, IRF, SFR ICAT, Angers, F-49000 France; 7Departments of Physics, Medical Pharmacology and Physiology, University of Missouri, Columbia, MO, 65211, USA; 8Department of Biotechnology and Food Technology, University of Johannesburg, Doornfontein, 2028, South AfricaCorrespondence: Kattesh V Katti, Department of RadiologyUniversity of Missouri-ColumbiaOne Hospital Drive, Columbia, Missouri, 65212, USA, Tel +1 573 882 5656, Fax +1 573 884 5679, Email KattiK@health.missouri.eduPurpose: Breast cancer is a significant global health issue, contributing to 15% of cancer-related deaths. Our laboratory has pioneered a novel approach, combining Ayurvedic principles with green nanotechnology, to develop a scientifically rigorous medical modality referred to as Nano-Ayurvedic Medicine, recently approved by the US Patents and Trademarks Office. Here in we report a new Nano-Ayurvedic medicine agent derived from gold nanoparticles encapsulated with phytochemicals from Ginkgo biloba plant (GB-AuNPs).Methods: We have developed biocompatible gold nanoparticles using electron-rich phytochemicals from Ginkgo biloba as reducing agent cocktail. Ginkgo biloba phytochemical-encapsulated gold nanoparticles (GB-AuNPs) were fully characterized, and their anticancer activity, including immunomodulatory profiles, were evaluated against breast (MDAMB-231) cancer cell lines.Results: Characterization revealed spherical morphology for GB-AuNPs and possessed optimum in vitro stability through high zeta potential of − 34 mV for optimum in vivo stability. The core size of GB-AuNPs of 19 nm allows for penetration into tumor cells through both EPR effects as well as through the receptor-mediated endocytosis. The Antitumor efficacy of this nano-ayurvedic medicine agent revealed strong antitumor effects of GB-AuNPs towards MDAMB-231. Our investigations reveal that GB-AuNPs enhance anti-tumor cytokines (IL-12, TNF-α, IFN-γ) and reduce pro-tumor cytokines (IL-10, IL-6), promoting the conversion of protumor M2 macrophages into M1-like macrophage antitumor phenotype. Cellular studies show that GB-AuNPs offer superior anti-tumor efficacy and a better safety profile against breast tumors compared to cisplatin.Conclusion: Our investigations have demonstrated that the nano-ayurvedic medicine agent, GB-AuNPs, treats cancers through an immunomodulatory mechanism facilitated by elevated levels of anti-tumor cytokines (TNF-α, IFN-γ and IL-12) with concomitant downregulation of pro-tumor cytokines expression (IL-6 and IL-10). The green nanotechnology approach for the development of nano-ayurvedic medicine agent (GB-AuNPs), as described in this paper, presents new and attractive opportunities for treating human cancers and other debilitating diseases and disorders.Keywords: Ginkgo biloba, gold nanoparticles, anticancer, Nano-Ayurvedic |