کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8944 610 2009 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy
چکیده انگلیسی

Selective drug delivery is an important approach with great potential for overcoming problems associated with the systemic toxicity and poor bioavailability of antineoplastic drugs. Nanomedicine plays a pivotal role by delivering drugs in a targeted manner to the malignant tumor cells thereby reducing the systemic toxicity of the anticancer drugs. The objective of this study was to prepare and characterize rapamycin loaded polymeric poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) that were surface conjugated with antibodies to epidermal growth factor receptor (EGFR), highly expressed on breast cancer cells, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) mediated cross linking agents. To potentiate the anticancer efficiency of the formulations, in vitro cytotoxicity of native rapamycin, rapamycin loaded nanoparticles and EGFR antibody conjugated rapamycin loaded nanoparticles (EGFR-Rapa-NPs) were evaluated on malignant MCF 7 breast cancer cell lines. IC50 doses as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay showed the superior antiproliferative activity of EGFR-Rapa-NPs over unconjugated nanoparticles and native rapamycin due to higher cellular uptake on malignant breast cancer cells. Cell cycle arrest and cellular apoptosis induced by the above formulations were confirmed by flow cytometry. Molecular basis of apoptosis studied by western blotting revealed the involvement of a cytoplasmic protein in activating the programmed cell death pathway. Thus it was concluded that EGFR-Rapa-NPs provide an efficient and targeted delivery of anticancer drugs, presenting a promising active targeting carrier for tumor selective therapeutic treatment in near future.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 30, Issue 29, October 2009, Pages 5737–5750
نویسندگان
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