Abstract
The present study evaluates poly (butyl cyanoacrylate) nanoparticles (PBCA-NPs), double-coated with Tween 80 and polyethylene glycol (PEG) 20,000 as a potential carrier system for overcoming P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)-mediated multidrug resistance (MDR) in cancer cell lines. Doxorubicin-loaded PBCA-NPs were prepared by the anionic polymerization method and were successively double-coated with Tween 80 and PEG 20000 at varied concentrations. MDR reversing potential was investigated by cellular uptake in P-gp overexpressing cell line. And, the outcomes were verified by modified MTT assay in P-gp or BCRP overexpressing cell lines. The findings from the cell uptake study indicate that double-coated PBCA-NPs significantly enhanced doxorubicin accumulation within the cells. MTT assays revealed that double-coated PBCA-NPs significantly potentiated the sensitivity of doxorubicin in P-gp overexpressing cells, in comparison to free doxorubicin, single-, and un-coated PBCA-NPs, respectively. Moreover, further increase in concentration with Tween 80, double-coated PBCA-NPs significantly enhanced the sensitivity of doxorubicin in BCRP overexpressing cell line, in comparison to single- and double-coated formulations (with lower concentration of Tween 80). Hence, it could be concluded that double-coated PBCA-NPs can be used as a potential carrier for enhancing doxorubicin accumulation in MDR cancer cells.
Highlights
Cancer is characterized by the uncontrolled growth and spread of cancerous cells and remains a major cause of death in the United States, causing over 600,000 fatalities annually
Nanoparticles Overcoming Multidrug Resistance in Cancers overexpression of drug efflux transporters (e.g., P-glycoprotein (P-gp/ABCB1), breast cancer resistant protein (BCRP/ABCG2), etc.) in cell lines has been discussed for describing the multidrug resistance (MDR) phenotype (Wang, Zhang, and Chen 2019)
It can be concluded that an overcoating with high molecular weight of polyethylene glycol (PEG) may impact the particle size of doxorubicin-loaded PBCA-NPs
Summary
Cancer is characterized by the uncontrolled growth and spread of cancerous cells and remains a major cause of death in the United States, causing over 600,000 fatalities annually. An Nanoparticles Overcoming Multidrug Resistance in Cancers overexpression of drug efflux transporters (e.g., P-glycoprotein (P-gp/ABCB1), breast cancer resistant protein (BCRP/ABCG2), etc.) in cell lines has been discussed for describing the MDR phenotype (Wang, Zhang, and Chen 2019). This leads to an elevated efflux of drugs from the cancer cells, subsequently limiting their intracellular accumulation. As a result, this occurrence has been interpreted as an obstacle to the success of chemotherapy (Gottesman, Fojo, and Bates 2002)
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