Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage

Scientific Reports
Sumit SiddharthChanakya N Kundu

Abstract

To overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitivity against DOX- resistance- breast cancer cells (MCF-7-DOX-R). These CS-DS and PLGA-PVA double coated DOX are spherical, stable, polydispersed and have zeta potential +2.89 mV. MCF-7- DOX-R cells were derived by exposing increasing doses of DOX in MCF-7 cells. These cells were resistance to 500 nM of DOX while parental cells were susceptible at 150 nM. The double coated NP caused more cytotoxicity in cancer and MCF-7-DOX-R cells without affecting the normal cells in comparison to DOX-loaded-PLGA-PVA-NP. These NP enhances the uptake of DOX in MCF-7-DOX-R cells and caused apoptosis by increasing apoptotic nuclei, Bax/Bcl-xL ratio, cleaved product PARP-1, tumor suppressor gene p21, p53, topoisomerase inhibition activity, DNA damage and decreasing the migratory potential of cells. An increased S phase arrest was noted in DOX and DOX- loaded- PLGA-PVA-NP treated cells but reduction of S phase and simultaneous increase of Sub-G1 was observed in do...Continue Reading

References

Jul 16, 2008·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Fu-Qiang HuHong Yuan
Aug 7, 2009·The Breast : Official Journal of the European Society of Mastology·R C F LeonardS Oliveros
Feb 22, 2012·Anti-cancer Agents in Medicinal Chemistry·Jose PradosAntonia Aranega

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Citations

Mar 17, 2021·International Journal of Pharmaceutics·Gabriela Rivera-HernándezMirna L Sánchez
Jul 3, 2021·Materials·Hernán CortésGerardo Leyva-Gómez
Jul 6, 2020·Drug Discovery Today·Mahdi ZeinaliMichael R Hamblin
Apr 15, 2020·Molecular Pharmaceutics·Aurore FraixSalvatore Sortino

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Methods Mentioned

BETA
FACS
X-ray
electrophoresis
flow cytometry

Software Mentioned

TriTek
Graph Pad Prism

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