کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
599332 1454274 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Optimizing the design and in vitro evaluation of bioreactive glucose oxidase-microspheres for enhanced cytotoxicity against multidrug resistant breast cancer cells
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی شیمی کلوئیدی و سطحی
پیش نمایش صفحه اول مقاله
Optimizing the design and in vitro evaluation of bioreactive glucose oxidase-microspheres for enhanced cytotoxicity against multidrug resistant breast cancer cells
چکیده انگلیسی


• Glucose oxidase-polymer microspheres of various sizes were prepared.
• H2O2 generation and cytotoxicity of GOX-MS increased with decreasing particle size.
• Small micron sized GOX-MS were taken up by MDR cancer cells.
• Small micron sized GOX-MS caused more membrane damage and lipid peroxidation.
• More membrane damage and lipid peroxidation occurred in MDR than in WT cells.

Glucose oxidase (GOX) encapsulated in alginate-chitosan microspheres (GOX-MS) was shown in our previous work to produce reactive oxygen species (ROS) in situ and exhibit anticancer effects in vitro and in vivo. The purpose of present work was to optimize the design and thus enhance the efficacy of GOX-MS against multidrug resistant (MDR) cancer cells. GOX-MS with different mean diameters of 4, 20 or 140 μm were prepared using an emulsification–internal gelation–adsorption–chitosan coating method with varying compositions and conditions. The GOX loading efficiency, loading level, relative bioactivity of GOX-MS, and GOX leakage were determined and optimal chitosan concentrations in the coating solution were identified. The influence of particle size on cellular uptake, ROS generation, cytotoxicity and their underlying mechanisms was investigated. At the same GOX dose and incubation time, smaller sized GOX-MS produced larger amounts of H2O2 in cell culture medium and greater cytotoxicity toward murine breast cancer MDR (EMT6/AR1.0) and wild type (EMT6/WT) cells. Fluorescence and confocal laser scanning microscopy revealed significant uptake of small sized (4 μm) GOX-MS by both MDR and WT cells, but no cellular uptake of large (140 μm) GOX-MS. The GOX-MS were equally effective in killing both MDR cells and WT cells. The cytotoxicity of the GOX formulations was positively correlated with membrane damage and lipid peroxidation. GOX-MS induced greater membrane damage and lipid peroxidation in MDR cells than the WT cells. These results suggest that the optimized, small micron-sized GOX-MS are highly effective against MDR breast cancer cells.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Colloids and Surfaces B: Biointerfaces - Volume 130, 1 June 2015, Pages 164–172
نویسندگان
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