%0 Journal Article %A Roy, Aniruddha %A Murakami, Mami %A Ernsting, Mark J. %A Hoang, Bryan %A Undzys, Elijus %A Li, Shyh-Dar %D 2014 %T Carboxymethylcellulose-Based and Docetaxel-Loaded Nanoparticles Circumvent P‑Glycoprotein-Mediated Multidrug Resistance %U https://acs.figshare.com/articles/journal_contribution/Carboxymethylcellulose_Based_and_Docetaxel_Loaded_Nanoparticles_Circumvent_P_Glycoprotein_Mediated_Multidrug_Resistance/2268778 %R 10.1021/mp400643p.s001 %2 https://ndownloader.figshare.com/files/3904792 %K vivo system %K Cellax treatment %K Pgp mRNA expression %K Pgp expression %K Cellax therapy %K vivo model %K EMT %K DTX %K antitumor activity %K 6.5 times %K anticancer agents %K drug resistance %K PEGylated carboxymethylcellulose conjugate %K IC 50 %K upregulate Pgp expression %K Pgp protein expression %X Taxanes are a class of anticancer agents with a broad spectrum and have been widely used to treat a variety of cancer. However, its long-term use has been hampered by accumulating toxicity and development of drug resistance. The most extensively reported mechanism of resistance is the overexpression of P-glycoprotein (Pgp). We have developed a PEGylated carboxymethylcellulose conjugate of docetaxel (Cellax), which condenses into ∼120 nm nanoparticles. Here we demonstrated that Cellax therapy did not upregulate Pgp expression in MDA-MB-231 and EMT-6 breast tumor cells, whereas a significant increase in Pgp expression was measured with native docetaxel (DTX) treatment. Treatment with DTX led to 4–7-fold higher Pgp mRNA expression and 2-fold higher Pgp protein expression compared with Cellax treatment in the in vitro and in vivo system, respectively. Cellax also exhibited significantly increased efficacy compared with that of DTX in a taxane-resistant breast tumor model. Against the highly Pgp expressing EMT6/AR1 cells, Cellax exhibited a 6.5 times lower IC50 compared with that of native DTX, and in the in vivo model, Cellax exhibited 90% tumor growth inhibition, while native DTX had no significant antitumor activity. %I ACS Publications