title: Gold-conjugated green tea nanoparticles for enhanced anti-tumor activities and hepatoprotection--synthesis, characterization and in vitro evaluation.
abstract: Green tea (GT)-based chemoprevention has shown promising results in various cancer models. However, the effective dose may not be far from the toxic dose because of inefficient systemic delivery and limited bio-availability of GT polyphenols. We have used GT polyphenols to successfully reduce gold to corresponding gold nanoparticles (NPs) in a single step; a process that fulfils all criteria of green nanotechnology as no "man-made" chemical other than gold acids are used. GT and (-) - epigallocatechin-3-gallate (EGCG) conjugated gold NPs (diameters <50 nm), showed remarkable stability, significantly rapid cellular uptake and excellent in vitro anti-oxidant activities. These NPs were observed to be selectively toxic towards cancer cells (Ehrlich's Ascites Carcinoma and MCF-7) while showing absolutely no lethality towards normal primary mouse hepatocytes. In cancer cells, NPs altered the redox status and limited Nrf2 activation by almost 50%. These NPs significantly decreased nuclear translocation of NF-κB, coupled with decreased phosphorylation of IĸB and down-regulation of NF-κB-dependent anti-apoptotic proteins Bcl2 and Akt in a dose-dependent manner, triggering onset of apoptosis. Culturing normal hepatocytes with tumor-conditioned media prompted apoptosis by increasing reactive oxygen species (ROS) and depleting the anti-oxidant defense mechanism of hepatocytes. Pre-treatment with NPs protected hepatocytes from tumor-induced cellular damage by scavenging excess ROS, increasing the levels of reduced glutathione and anti-oxidant enzymes. There was evidence of decreased Bax/Bcl2 ratio and active Caspase 3 levels in these hepatocytes, indicating apoptosis escape. Nanoformulations of GT-based polyphenols might serve as an operative platform for effective delivery, increased bio-availability, enhanced effects and minimal chemotherapy-associated toxicities.
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India.
authors: Sudeshna
authors: S
authors: Mukherjee
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India.
authors: Sayan
authors: S
authors: Ghosh
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India.
authors: Dipesh Kr
authors: DK
authors: Das
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India.
authors: Priyanka
authors: P
authors: Chakraborty
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India.
authors: Sreetama
authors: S
authors: Choudhury
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India.
authors: Payal
authors: P
authors: Gupta
authors: Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Salt Lake, Sector III, Kolkata-700098, India.
authors: Arghya
authors: A
authors: Adhikary
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Salt Lake, Sector III, Kolkata-700098, India.
authors: Sanjit
authors: S
authors: Dey
authors: Department of Physiology, University of Calcutta; UCSTA, 92, Acharya Prafulla Chandra Road, Kolkata-700009, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Salt Lake, Sector III, Kolkata-700098, India. Electronic address: sreyasaha@gmail.com.
authors: Sreya
authors: S
authors: Chattopadhyay
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006046:Gold / Q000737:chemistry; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D061986:MCF-7 Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D013662:Tea / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D013662:Tea; D006046:Gold; D002392:Catechin; C045651:epigallocatechin gallate
keywords: Apoptosis; EGCG; Green tea; Hepatotoxicity; NF-κB; Nanochemoprevention; Nrf2