title: Tailored-CuO-nanowire decorated with folic acid mediated coupling of the mitochondrial-ROS generation and miR425-PTEN axis in furnishing potent anti-cancer activity in human triple negative breast carcinoma cells.
abstract: Metal oxide nanoparticles are the forthcoming anti-tumor therapeutics and provide a versatile platform in the development of therapeutic approaches for drug-resistant cancers such as triple negative breast cancer (TNBC). Copper oxide nanoparticles have been characterized as anti-cancer agents but its toxicity has been a matter of concern. Herein, we have developed a targeted CuO Nanowire fabricated with Folic acid (CuO-Nw-FA) that enables enhanced cellular uptake in TNBC cells without imparting significant toxicity in normal cellular system. In the present study, we enumerated that CuO-Nw-FA caused mitochondrial-dependent apoptosis in MDAMB-231 cells. Furthermore, CuO-Nw-FA mediated cytosolic retardation of NF-κB favoured inactivation of miR-425 and henceforth activated PTEN to induce apoptosis in TNBC cells. Simultaneously, CuO-Nw-FA also restricted the in-vitro cell migration through the miR-425/PTEN axis via pFAK. Studies extended to ex-ovo and in-vivo mice models further validated the efficacy of CuO-Nw-FA. Additionally, the accumulations of nanoparticles in tumor as well as different organs in mice were examined by in-vivo biodistribution and ex-vivo optical imaging studies. Thus our results cumulatively propose that CuO-Nw-FA cross-talks two distinct signalling pathways to induce apoptosis and retard migration in TNBC cells and raises the possibility for the use of CuO-Nw-FA as a potent anti-tumor agent.
authors.affiliation: Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Sector III, Salt Lake, Kolkata, 700098, WB, India.
authors.forename: Manisha
authors.initials: M
authors.lastname: Ahir
authors.affiliation: Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Sector III, Salt Lake, Kolkata, 700098, WB, India.
authors.forename: Saurav
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Sector III, Salt Lake, Kolkata, 700098, WB, India.
authors.forename: Soumendu
authors.initials: S
authors.lastname: Karmakar
authors.affiliation: Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Sector III, Salt Lake, Kolkata, 700098, WB, India.
authors.forename: Ayan
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Physiology, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata, 700009, WB, India.
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, P-1/12, Calcutta Improvement Trust Scheme VII M, Kolkata, 700054, WB, India.
authors.forename: Swatilekha
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Physiology, University of Calcutta, 92 Acharya Prafulla Chandra Road, Kolkata, 700009, WB, India.
authors.forename: Sreya
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Sector III, Salt Lake, Kolkata, 700098, WB, India.
authors.forename: Prasun
authors.initials: P
authors.lastname: Patra
authors.affiliation: Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, JD-2, Sector III, Salt Lake, Kolkata, 700098, WB, India. Electronic address: adhikaryarghya@gmail.com.
authors.forename: Arghya
authors.initials: A
authors.lastname: Adhikary
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D002642:Chick Embryo; D003300:Copper / Q000737:chemistry*; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D053770:Nanowires; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C555677:MIRN425 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D003300:Copper; D005492:Folic Acid; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C030973:cupric oxide
keywords: Apoptosis; Copper oxide nanowire; Migration; NF-κB; Reactive oxygen species; miR-425