title: EGF-modified mPEG-PLGA-PLL nanoparticle for delivering doxorubicin combined with Bcl-2 siRNA as a potential treatment strategy for lung cancer.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  We conclude that co-delivery of Dox and Bcl-2-siRNA by tumor-targeted EGF-PEAL NPs could significantly inhibit lung cancer growth.
authors.affiliation: a State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China and.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China and.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China and.
authors.forename: Liubing
authors.initials: L
authors.lastname: Qin
authors.affiliation: a State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China and.
authors.forename: Hao
authors.initials: H
authors.lastname: Fu
authors.affiliation: a State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China and.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Fang
authors.affiliation: b Department of General Surgery , School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Baoshan
authors.initials: B
authors.lastname: Han
authors.affiliation: a State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China and.
authors.forename: Yourong
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C574222:monomethoxy (polyethylene glycol)-poly(lactide-co-glycolide)-poly(lysine); D011107:Polylysine; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor; D004317:Doxorubicin
keywords: Bcl-2 gene; drug delivery; epidermal growth factor; lung cancer; nanoparticles