4.6 Article

Doxorubicin delivery by magnetic nanotheranostics enhances the cell death in chemoresistant colorectal cancer-derived cells

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出版社

ELSEVIER
DOI: 10.1016/j.ejps.2020.105681

关键词

Colorectal cancer therapy; Magnetic nanoparticles; Doxorubicin; Drug delivery; Apoptosis

资金

  1. Instituto Nacional del Cancer (Asistencia Financiera III-2016-2017) [RESOL-2016-1006-E-APN-MS]
  2. Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [PIP112-201101-00409]
  3. Universidad Nacional del Sur [PGI 24/ZQ14, PGI 24/ZB80, PGI 24/B230, PGI 24/B303]
  4. Agencia Nacional de Promocion Cientifica, Tecnologica y de la Innovacion, Argentina [PICT 2015 0932]
  5. CONICET

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The study evaluated the aptitude of magnetic nanotheranostics for colorectal cancer treatment by enhancing cell death through the administration of DOXO via MNPs, further confirming its achievement of apoptosis through chromatin compaction and cytoplasmic protrusions. Additionally, MNPs were found to possess potential characteristics as magnetic therapy and vectoring tools.
Colorectal cancer (CRC) is a major cause of cancer death with a high probability of treatment failure. Doxorubicin (DOXO) is an efficient antitumor drug; however, most CRC cells show resistance to its effects. Magnetic nanoparticles (MNPs) are potential cancer management tools that can serve as diagnostic agents and also can optimize and personalize treatments. This work aims to evaluate the aptitude of magnetic nanotheranostics composed of magnetite (Fe3O4) nanoparticles coated with folic acid intended to the sustained release of DOXO. The administration of DOXO by means of these MNPs resulted in the enhancement of cell death respect to the free drug administration. Chromatin compaction and cytoplasmic protrusions were observed. Mitochondrial transmembrane potential disruption and increased PARP protein cleavage confirmed apoptosis. The nanosystem was also tested as a vectoring tool by exposing it to the stimuli of a static magnetic field in vitro. CRC-related magnetic nanotechnology still remains in pre-clinical trials. In this context, this contribution expands the knowledge of the behavior of MNPs in contact with in vitro models and proposes the nanodevices studied here as potential theranostic agents for the monitoring of the progress of CRC and the evolution of its treatment.

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