Iron-oxide nanoparticles target intracellular HSP90 to induce tumor radio-sensitization

Biochimica Et Biophysica Acta. General Subjects
Neena G ShetakeB N Pandey

Abstract

Nanoparticle-based therapies have emerged as a promising approach to overcome limitations of conventional chemotherapy. Present study investigates the potential of oleic acid-functionalized iron-oxide nanoparticles (MN-OA) to enhance the radiation response of fibrosarcoma tumor and elucidates its underlying mechanism. Various cellular and molecular assays (e.g. MTT, clonogenic, cell cycle analysis, cell death, DNA damage/repair) and tumor growth kinetics were employed to investigate the mechanism of MN-OA induced radio-sensitization. Mouse (WEHI-164) and human (HT-1080) fibrosarcoma cells treated with MN-OA and gamma-radiation (2 Gy) showed a significant decrease in the cell proliferation. Combination treatment showed significant decrease in clonogenic survival of WEHI-164 cells and was found to induce cell cycle arrest, apoptosis and mitotic catastrophe. The mechanism of radio-sensitization was found to involve binding of MN-OA with HSP90, resulting in down-regulation of its client proteins, involved in cell cycle progression (Cyclin B1 and CDC2) and DNA-double strand break repair (e.g. RAD51 and BRCA1). Consistently, longer persistence of DNA damage in cells treated with MN-OA and radiation was observed in the form of γ-H2AX ...Continue Reading

Citations

Oct 4, 2020·IET Nanobiotechnology·Hasnat Tariq, Syed Ali Imran Bokhari
Mar 15, 2020·Nanomaterials·Hainan SunShumei Zhai
Jul 3, 2021·International Journal of Molecular Sciences·Roxana Cristina PopescuMarlon R Veldwijk

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