Targeted delivery of doxorubicin into tumor cells by nanostructured lipid carriers conjugated to anti-EGFRvIII monoclonal antibody

سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 197

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شناسه ملی سند علمی:

NANOTEC05_004

تاریخ نمایه سازی: 28 خرداد 1400

چکیده مقاله:

Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the EGF receptor in many human tumors. This variant is tumor specific and highly immunogenic, thus, it can be used as a target for targeted drug delivery toward tumor cells. The major aim of this study was to develop an EGFRvIII-mediated drug delivery system by anti-EGFRvIII monoclonal antibody (MAb) conjugated to doxorubicin (Dox)-loaded nanostructured lipid carriers (NLC) to enhance the targeting specificity and cytotoxic effect of Dox on EGFRvIII-overexpressing cell line. In our study, Dox was chosen as a hydrophobic cytotoxic drug and drug-loaded nanostructured lipid carriers (Dox-NLC) was prepared by solvent emulsification/evaporation method. In order to conjugate anti-EGFRvIII MAb to Dox-NLC, DSPEPEG۲۰۰۰-NHS (۱,۲-distearoylphosphatidylethanolamine–polyethylene glycol ۲۰۰۰–NHS) was used as a linker. Physicochemical characteristics of antibody conjugated Dox-NLC (MAb-Dox-NLC), including particle size, zeta potential, entrapment efficiency and in vitro Dox release were investigated. Cytotoxicity of MAb-Dox-NLC against NIH-۳T۳ and HC۲ ۲۰d۲/c (EGFRvIII-transfected NIH-۳T۳) cell lines was evaluated. The MAb-Dox-NLC appeared to enhance the cytotoxic activity of targeted NLC against HC۲ ۲۰d۲/c cells. The cellular uptake percentage of targeted NLC by HC۲ ۲۰d۲/c cells was higher than that of NIH-۳T۳ cells, indicating that EGFRvIII can specifically target HC۲ ۲۰d۲/c cells. In conclusion, antiEGFRvIII MAb-targeted NLC may be considered as an effective nanocarrier for targeted drug delivery.

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نویسندگان

Saeideh Abdolahpour

Department of Medical Biochemistry Faculty of Medicine, Tehran University of Medical Sciences Tehran, Iran

Maliheh Paknejad

Department of Medical Biochemistry Faculty of Medicine, Tehran University of Medical Sciences Tehran, Iran

Tayebeh Toliyat

Department of Pharmaceutics Faculty of Pharmacy, Tehran University of Medical Sciences Tehran, Iran