Overcoming cancer multidrug resistance by codelivery of doxorubicin and verapamil with hydrogel nanoparticles.
The efficacy of chemotherapy is often inhibited by multidrug resistance (MDR). A highly engineerable hydrogel nanoparticle (NP) serves as a carrier for the optimal codelivery to tumor cells of the chemodrug, doxorubicin (Dox) and the chemosensitizer, verapamil (Vera), aiming at alleviating tumor MDR. The hydrogel NPs are prepared via the copolymerization of acrylamide and 2-carboxyethyl acrylate. Dox and Vera are post-loaded into the respective NPs, with drug loading around 7.7 wt% and 8.0 wt%, respectively. The codelivery of Dox-NPs and Vera-NPs increases the intracellular accumulation of Dox, and significantly enhances the cell killing ability of Dox with respect to NCI/ADR-RES cells in vitro. These findings suggest that such codelivery nanoplatforms provide a promising route for overcoming tumor MDR.
Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
Ming
M
Qin
Yong-Eun Koo
YE
Lee
Aniruddha
A
Ray
Raoul
R
Kopelman
D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D014700:Verapamil / Q000008:administration & dosage
D000970:Antineoplastic Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D004317:Doxorubicin; D014700:Verapamil
cancer therapy; doxorubicin; hydrogel nanoparticles; multidrug resistance; verapamil