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Mechanism of Anti-Cancer Activity of Benomyl Loaded Nanoparticles in Multidrug Resistant Cancer Cells

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Title Mechanism of Anti-Cancer Activity of Benomyl Loaded Nanoparticles in Multidrug Resistant Cancer Cells
 
Creator KINI, S
BAHADUR, D
PANDA, D
 
Subject DRUG-DELIVERY
BREAST-CANCER
POLYALKYLCYANOACRYLATE NANOPARTICLES
POLYMERIC NANOPARTICLES
CHITOSAN NANOPARTICLES
CONTROLLED-RELEASE
P-GLYCOPROTEIN
CYCLOSPORINE-A
GENE DELIVERY
IN-VITRO
Benomyl
Chitosan
Poly(D, L-lactide-co-glycolide) Nanoparticles
Anticancer Therapy
Microtubules
Apoptosis
Drug Resistance
 
Description Polymeric chitosan-poly(D, L-lactide-co-glycolide) nanoparticles loaded with benomyl as anticancer drug formulation against multidrug-resistant EMT6/AR1 cells were synthesized by amine-carboxylate reaction. Using transmission electron microscopy, the average size of chitosan-poly(D, L-lactide-co-glycolide) nanoparticles and benomyl-encapsulated polymeric chitosan-poly(D, L-lactide-co-glycolide) nanoparticles was estimated to be 155 +/- 20 nm and 160 +/- 25 nm, respectively. Fourier transform infrared spectroscopy revealed that poly(D, L-lactide-co-glycolide) and chitosan are linked by covalent bonds. Zeta potentials of benomyl-encapsulated polymeric chitosan-poly(D, L-lactide-co-glycolide) nanoparticles at pH 4, 7.2, and 10 were 30 +/- 1.8, 19 +/- 0.65, and -22 +/- 0.15 mV, respectively, indicating the formation of stable, hydrophilic nanoparticles. The release of benomyl from benomyl-encapsulated polymeric chitosan-poly(D, L-lactide-co-glycolide) nanoparticles followed pH-dependent kinetics. The uptake of fluorescein isothiocyanate-labeled chitosan-poly(D, L-lactide-co-glycolide) nanoparticles was concentration-dependent in both MCF-7 and multidrug-resistant EMT6/AR1 cells. EMT6/AR1 cells showed 10-fold higher resistance to benomyl compared to MCF-7 cells; in contrast, benomyl-encapsulated polymeric chitosan-poly(D, L-lactide-co-glycolide) nanoparticles effectively inhibited proliferation of MCF-7 and EMT6/AR1 cells with a half-maximal inhibitory concentration of 4 +/- 0.5 and 9 +/- 0.5 mu M, respectively. In the presence of a P-glycoprotein inhibitor, the activity of benomyl was increased, suggesting that benomyl is a substrate for P-glycoprotein. Further, benomyl-encapsulated polymeric chitosan-poly(D, L-lactide-co-glycolide) nanoparticles depolymerized microtubules both in interphase and mitosis. It blocked cell cycle progression at G2/M and induced apoptosis in EMT6/AR1 cells, suggesting that benomyl-encapsulated polymeric chitosan-poly(D, L-lactide-co-glycolide) nanoparticles have chemotherapeutic activity against multidrug-resistant cancer cells.
 
Publisher AMER SCIENTIFIC PUBLISHERS
 
Date 2016-01-15T10:00:14Z
2016-01-15T10:00:14Z
2015
 
Type Article
 
Identifier JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, 11(5)877-889
1550-7033
1550-7041
http://dx.doi.org/10.1166/jbn.2015.1998
http://dspace.library.iitb.ac.in/jspui/handle/100/18315
 
Language en