Phytochemicals occluded in tea have been extensively used as dietary supplements and as natural pharmaceuticals in the treatment of various diseases including human cancer. Results on the reduction capabilities of phytochemicals present in tea to reduce gold salts to the corresponding gold nanoparticles are presented in this paper. The phytochemicals present in tea serve a dual role as effective reducing agents to reduce gold and also as stabilizers to provide a robust coating on the gold nanoparticles in a single step. The tea-generated gold nanoparticles (T-AuNPs), have demonstrated remarkable in vitro stability in various buffers including saline, histidine, HSA, and cysteine solutions. T-AuNPs with phytochemical coatings have shown significant affinity toward prostate (PC-3) and breast (MCF-7) cancer cells. Results on the cellular internalization of T-AuNPs through endocytosis into the PC-3 and MCF-7 cells are presented. The generation of T-AuNPs follows all principles of green chemistry and T-AuNPs have been found to be non toxic as assessed through MTT assays. No ‘man made’ chemicals, other than gold salts, are used in this truly biogenic, green nanotechnological process thus paving the way for excellent opportunities for their application in molecular imaging and therapy.

Development of cancer receptor-specific gold nanoparticles will allow efficient targeting/optimum retention of engineered gold nanoparticles within tumors and thus provide synergistic advantages in oncology as it relates to molecular imaging and therapy. Bombesin (BBN) peptides have demonstrated high affinity toward gastrin-releasing peptide (GRP) receptors in vivo that are overexpressed in prostate, breast, and small-cell lung carcinoma. We have synthesized a library of GRP receptor-avid nanoplatforms by conjugating gold nanoparticles (AuNPs) with BBN peptides. Cellular interactions and binding affinities (IC ₅₀ ) of AuNP–BBN conjugates toward GRP receptors on human prostate cancer cells have been investigated in detail. In vivo studies using AuNP–BBN and its radiolabeled surrogate ¹⁹⁸ AuNP–BBN, exhibiting high binding affinity (IC ₅₀ in microgram ranges), provide unequivocal evidence that AuNP–BBN constructs are GRP-receptor-specific showing accumulation with high selectivity in GRP-receptor-rich pancreatic acne in normal mice and also in tumors in prostate-tumor-bearing, severe combined immunodeficient mice. The i.p. mode of delivery has been found to be efficient as AuNP–BBN conjugates showed reduced RES organ uptake with concomitant increase in uptake at tumor targets. The selective uptake of this new generation of GRP-receptor-specific AuNP–BBN peptide analogs has demonstrated realistic clinical potential in molecular imaging via x-ray computed tomography techniques as the contrast numbers in prostate tumor sites are severalfold higher as compared to the pretreatment group (Hounsfield unit = 150).

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.

Purpose: The overarching objective of this investigation was to investigate the intervention of green nanotechnology to transform the ancient holistic Ayurvedic medicine scientifically credible through reproducible formulations and rigorous pre-clinical/clinical evaluations. Methods: We provide, herein, full details: (i) on the discovery and full characterization of gold nanoparticles-based Nano Swarna Bhasma (henceforth referred to as NSB drug); (ii) In vitro anti-tumor properties of NSB drug in breast tumor cells; (iii) pre-clinical therapeutic efficacy studies of NSB drug in breast tumor bearing SCID mice through oral delivery protocols and (iv) first results of clinical translation, from mice to human breast cancer patients, through pilot human clinical trials, conducted according to the Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (abbreviated as AYUSH) regulatory guidelines of the Government of India in metastatic breast cancer patients. Results: The preclinical in vitro and in vivo investigations, in breast tumor bearing mice, established unequivocally that the NSB Nano-Ayurvedic medicine-gold nanoparticles-based drug is highly effective in controlling the growth of breast tumors in a dose dependent fashion in vivo. These encouraging pre-clinical results prompted us to seek permission from the Indian Government’s holistic medicine approval authority, AYUSH, for conducting clinical trials in human patients. Patients treated with the NSB drug capsules along with the “standard of care treatment” (Arm B) exhibited 100% clinical benefits when compared to patients in the treatment Arm A, thus indicating the tremendous clinical benefits of NSB drug in adjuvant therapy. Conclusion: We have succeeded in clinically translating, from mice to humans, in using proprietary combinations of gold nanoparticles and phytochemicals to develop the Nano-Ayurvedic drug: Nano Swarna Bhasma (NSB), through innovative green nanotechnology, for treating human metastatic breast cancer patients.