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- W2917595589 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 foci. The efficacy and mechanism of MN-OA-induced radio-sensitization was also validated in an immuno-competent murine fibrosarcoma model. This study reveals the key role of HSP90 in the mechanism of tumor radio-sensitization by MN-OA. Present work provides a deeper understanding about the mechanism of MN-OA-induced tumor radiosensitization, highlighting the role of HSP90 protein. In addition to diagnostic and magnetic hyperthermia abilities, present remarkable radiosensitizing activity of MN-OA would further excite the clinicians to test its anti-cancer potential." @default.
- W2917595589 created "2019-03-02" @default.
- W2917595589 creator A5027254778 @default.
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- W2917595589 date "2019-05-01" @default.
- W2917595589 modified "2023-09-26" @default.
- W2917595589 title "Iron-oxide nanoparticles target intracellular HSP90 to induce tumor radio-sensitization" @default.
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- W2917595589 doi "https://doi.org/10.1016/j.bbagen.2019.02.010" @default.
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