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

被引：75

作者：

Ahir, Manisha ^{[1
]}

Bhattacharya, Saurav ^{[1
]}

Karmakar, Soumendu ^{[1
]}

Mukhopadhyay, Ayan ^{[1
]}

Mukherjee, Sudeshna ^{[2
]}

Ghosh, Swatilekha ^{[3
]}

Chattopadhyay, Sreya ^{[2
]}

Patra, Prasun ^{[1
]}

Adhikary, Arghya ^{[1
]}

机构：

[1] Univ Calcutta, Ctr Res Nanosci & Nanotechnol, Kolkata 700098, WB, India

[2] Univ Calcutta, Dept Physiol, Kolkata 700009, WB, India

[3] Bose Inst, Div Mol Med, Kolkata 700054, WB, India

来源：

BIOMATERIALS | 2016年 / 76卷

关键词：

Copper oxide nanowire; Reactive oxygen species; NF-kappa B; miR-425; Apoptosis; Migration; ADHESION KINASE EXPRESSION; PROTEIN-TYROSINE KINASE; FOLATE-RECEPTOR; TARGETED DELIVERY; MODEL SYSTEM; IN-VITRO; CANCER; NANOPARTICLES; METASTASIS; PTEN;

D O I：

10.1016/j.biomaterials.2015.10.044

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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-kappa B 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 NBC cells and raises the possibility for the use of CuO-Nw-FA as a potent anti-tumor agent. (c) 2015 Elsevier Ltd. All rights reserved.

引用

页码：115 / 132

页数：18

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