Overcoming Multidrug Resistance of Breast Cancer Cells by the Micellar Doxorubicin Nanoparticles of mPEG-PCL-Graft-Cellulose

Abstract

The amphiphilic block copolymer methoxy-poly(ethylene glycol)-poly(epsilon-caprolactone) (mPEG-PCL) was grafted to 2-hydroxyethyl cellulose (HEC) to produce nano-sized micellar nanoparticles. The nanoparticles were loaded with anti-tumor drug, doxorubicin (DOX) and the size of the DOX-loaded nanoparticles were determined by dynamic light scattering (DLS) in aqueous solution to be from 197.4 to 230 nm. The nanoparticles subjected to co-culture with macrophage cells showed that these nanoparticles used as drug carrier are not recognized as foreign bodies. Overexpression of P-glycoprotein (P-gp) is an important factor in the development of multidrug resistance (MDR) in many cancer cells. In this study, Western blot and Rhodamine 123 were used to monitor the relative P-glycoprotein expression in human breast cancer cell lines MCF-7/WT and MCF-7/ADR. The endocytosis of the DOX-loaded nanoparticles by breast cancer cells is more efficient observed under a confocal laser scanning microscopy (CLSM) and a flow cytometry in MCF7/ADR cells, compared to the diffusion of the free drug into the cytoplasm of cells. Based on these findings, we concluded that the nanoparticles made from mPEG-PCL-g-cellulose were effective in overcoming P-gp efflux in MDR breast cancer cells.

Polysaccharide-Based Micelles for Drug Delivery

“…Other work has focused on the design and synthesis of cellulose-based micelles; however, how these systems can be applied to the field of drug delivery has not yet been described. Such systems include HPC-polycaprolactone [ 98 ] and cellulose-C 15 -pyrene micelle. Of interest, micelles prepared from cellulose-C 15 -pyrene with longer cellulose chains (M w = 4860 g/mol, number average degree of polymerization (D n ) = 30) were smaller in size (~40.0 nm, monolayer micelle) relative to those prepared from short chain cellulose (M w = 2106 g/mol, Dn = 13) (~108.8 nm, multilayer micelle) [ 119 ].…”

Assessment of the relative performance of a confined impinging jets mixer and a multi-inlet vortex mixer for curcumin nanoparticle production

“…It has been widely demonstrated that particles with size around or less than 200 nm possess a number of unique advantageous properties, including increased circulation time in blood [1,2], capability of crossing restrictive biological barriers via transcytosis or the paracellular pathway [3,4], ability to circumvent multidrug resistance [5][6][7] and enhanced permeability and retention effect (EPR) [8]. However, despite the availability of a wide range of techniques for producing organic pharmaceutical nanoparticles, there has not yet been a pragmatic and efficient nanoparticle technology that can consistently engineer nanoparticles to predetermined specifications.…”

Synthesis, characterization, and micellar behaviors of hydroxyethyl cellulose-graft-poly(lactide/ε-caprolactone/p-dioxanone)

“…The self-assemblies based on amphiphilic polymers are excellent carriers of waterinsoluble drugs and functional materials (Guo et al 2012). To date, the amphiphilic polymeric materials have been applied in a broad range of fields, such as drug delivery (Chang et al 2008;Chen et al 2011b;Miller et al 2013;Wang et al 2014b), bioimaging (Lu et al 2012;Zhang et al 2013) and sensing (Gong et al 2014;Wang et al 2012a). Lately, in response to the shortage of petroleum resources and the growing need for sustainable development, the natural polysaccharide-based amphiphiles have received a great deal of interest because of their promising properties, e.g., ready availability, good biocompatibility, biodegradability and nontoxicity (Hassani et al 2012).…”