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Int J Mol Sci ; 21(19)2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-33007844

RESUMEN

This study aims to investigate whether ionizing radiation combined with doxorubicin-conjugated iron oxide nanoparticles (NP-DOX) improves the internalization and cytotoxic effects of the nano-carrier-mediated drug delivery in MG-63 human osteosarcoma cells. NP-DOX was designed and synthesized using the co-precipitation method. Highly stable and crystalline nanoparticles conjugated with DOX were internalized in MG-63 cells through macropinocytosis and located in the perinuclear area. Higher nanoparticles internalization in MG-63 cells previously exposed to 1 Gy X-rays was correlated with an early accumulation of cells in G2/M, starting at 12 h after treatment. After 48 h, the application of the combined treatment led to higher cytotoxic effects compared to the individual treatment, with a reduction in the metabolic capacity and unrepaired DNA breaks, whilst a low percent of arrested cells, contributing to the commitment of mitotic catastrophe. NP-DOX showed hemocompatibility and no systemic cytotoxicity, nor histopathological alteration of the main organs.


Asunto(s)
Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Osteosarcoma/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Terapia Combinada , Doxorrubicina/química , Endocitosis/efectos de los fármacos , Endocitosis/efectos de la radiación , Compuestos Férricos/química , Compuestos Férricos/farmacología , Humanos , Mitosis/efectos de los fármacos , Mitosis/efectos de la radiación , Osteosarcoma/patología , Osteosarcoma/radioterapia , Radiación Ionizante
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