EGF-modified mPEG-PLGA-PLL nanoparticle for delivering doxorubicin combined with Bcl-2 siRNA as a potential treatment strategy for lung cancer

Autor:	Hao Fu, Yourong Duan, Yiwei Fang, Xiangyu Zhang, Qi Wang, Liubing Qin, Baoshan Han
Rok vydání:	2016
Předmět:	0301 basic medicine Biodistribution Materials science Lung Neoplasms Polyesters Pharmaceutical Science Mice Nude Antineoplastic Agents Pharmacology Polyethylene Glycols 03 medical and health sciences Mice 0302 clinical medicine Epidermal growth factor Cell Line Tumor medicine Animals Doxorubicin Polylysine Tissue Distribution Particle Size RNA Small Interfering Cytotoxicity Drug Carriers Mice Inbred BALB C Epidermal Growth Factor technology industry and agriculture General Medicine respiratory system 030104 developmental biology Cell killing Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Drug delivery Cancer cell Nanoparticles Drug carrier medicine.drug
Zdroj:	Drug delivery. 23(8)
ISSN:	1521-0464
Popis:	Nanoparticles (NPs) have been widely used as carriers to deliver siRNA and chemotherapeutic agents. Bcl-2 siRNA has been widely used to induce cancer cell apoptosis, and doxorubicin (Dox) can destroy cancer cells by binding with cancer cell DNA.To investigate the therapeutic effect on lung cancer of simultaneously delivering Dox and Bcl-2-siRNA using epidermal growth factor (EGF) modified monomethoxy (polyethylene glycol)-poly (D, L-lactide-co-glycolide)-poly(L-lysine) (mPEG-PLGA-PLL, PEAL) NPs (EGF-PEAL).EGF-PEAL NPs were characterized with respect to size, zeta potential and morphology. Cytotoxicity and drug (or siRNA) loading capacity of EGF-PEAL NPs were analyzed. Cellular uptake, drug release profile, cell killing effects of Dox and Bcl-2-siRNA-loaded EGF-PEAL NPs were assessed. Biodistribution and therapeutic effects of Dox and Bcl-2-siRNA EGF-PEAL NPs were evaluated in H1299 tumor-bearing mice.EGF-PEAL NPs or PEAL NPs had nearly negligible cytotoxicity toward H1299 cells. Dox and Bcl-2-siRNA gradually released from EGF-PEAL NPs and exhibited sustained release patterns. Dox and Bcl-2-siRNA-loaded NPs were taken up by cells and induced the apoptosis of H1299 cells more effectively than using Dox or Bcl-2 siRNA alone. With the intravenous injection of PEAL NPs into H1299 xenografted mice, we found that combination treatment suppressed lung cancer growth and reduced Bcl-2 expression in tumor tissue, and EGF-PEAL NPs concentrated in lung tumor much more than non-targeted PEAL NPs.We conclude that co-delivery of Dox and Bcl-2-siRNA by tumor-targeted EGF-PEAL NPs could significantly inhibit lung cancer growth.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ed2cc02eb7cb6f7c2e5e92417edfff4 https://pubmed.ncbi.nlm.nih.gov/26739487 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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