Abstract 5659: Surface modification of epirubicin-loaded PLGA nanoparticle with biotinylated chitosan enhances anti-cancer efficacy in breast cancer cells.

Abstract

Abstract Nanoparticle (NP) delivery systems in cancer therapies provide better penetration of therapeutic and diagnostic substances within the body at a reduced risk in comparison with conventional cancer therapies. This is to continue our earlier work on the poly(D,L-lactide-co-glycolide) (PLGA) NPs with biotinylated chitosan (Bio-CS) modification, the modified PLGA NPs were further used as an epirubicin (EPB) carrier to enhance cancer targeting activity and to overcome multidrug resistance (MDR) in adriamycin-resistance human breast cancer cell line (MCF-7/ADM). In this study, Bio-CS were synthesized and characterized. The degree of substitution (DS), as defined as the number of biotin per 100 anhydroglucose units of CS, was determined by 1H-NMR and ICP. EPB-loaded PLGA NPs were prepared by a solvent evaporation technique (W1/O/W2). The PLGA NPs surface was modified by Bio-CS via covalent binding. PLGA NPs of (231.4±21.0) nm in diameter characterized by laser light scattering technique, scanning electron microscopy are spherical and its drug encapsulation efficiency is (84.1±3.4)%. Zeta potential of unmodified NP was measured to be negative -(21.21±2.13) mV. The positive zeta potential of modified NPs represented the presence of CS on the surface of the modified NPs. Modified NPs were characterized for surface chemistry by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR). N region corresponding to the primary amide of CS and S region corresponding to the biotin meant that PLGA NPs were successfully surface-modified with Bio-CS. The 31% of surface DS biotin of Bio-CS modified PLGA NPs were determined and the value was (1.36 ± 0.34) μmol/100mg. In vitro drug release studies showed that Bio-CS modified NPs had many advantages, such as prolonged drug release property and decreased burst release, in comparison to the unmodified NPs, and the modified NPs achieved relatively constant release kinetics. For cytotoxicity evaluation in vitro, the MCF-7/ADM cells were treated with free EPB, EPB-loaded PLGA NP and EPB-loaded NP with Bio-CS modification, respectively, at a same concentration of 150μg/mL, for 4, 24, 48 and 72 h. We found that Bio-CS modified NPs markedly increased EPB anti-cancer activity, compared to the unmodified NPs. Flowcytometry and confocal laser scanning microscopy revealed that Bio-CS-modified NPs exhibited greater extent of cellular uptake than unmodified NP and free EPB at 48h. Moreover, the uptakes of CS-modified NPs were significantly increased and cell viabilities were dramatically decreased in the MCF-7/ADM cells, compared to the free EPB and PLGA NPs. In summary, the NPs by surface modification with Bio-CS significantly enhanced anti-cancer drug EPB delivery, increased drug efficacy, and thus this system will have great potential for cancer chemotherapy. Citation Format: Hongli Chen, Rui Liu, Wenbin Nan, Yongxue Wang, Yinsong Wang, Wancai Yang, Wancai Yang. Surface modification of epirubicin-loaded PLGA nanoparticle with biotinylated chitosan enhances anti-cancer efficacy in breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5659. doi:10.1158/1538-7445.AM2013-5659 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.