title: Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system.
abstract: BACKGROUND
  Cardiotoxicity and myelosuppression of etoposide (ETP) limited its clinical application. Targeted drug delivery system could deliver anticancer agents to the target cancerous cells, thus reducing their toxicity.
  
  
  OBJECTIVE
  In this study, folate (FA) was applied for the construction of nanostructured lipid carriers (NLCs), and used for targeted delivery of ETP to tumors overexpresses the FA receptors.
  
  
  METHODS
  FA-poly (ethylene glycol)-distearoylphosphatidylethanolamine was synthesized. FA decorated and ETP-loaded NLCs (FA-ETP-NLCs) were prepared and the formulation was optimized by Box-Behnken design. Their particle size (PS), zeta potential and drug encapsulation efficiency (EE) was evaluated. In vitro cytotoxicity studies of FA-ETP-NLCs were tested in CT26, SGC7901, NCI-H209 cell lines. In vivo antitumor efficacies of the carriers were evaluated on mice bearing CT26 cells xenografts.
  
  
  RESULTS
  The optimum FA-ETP-NLCs formulations had a PS of 120.86 nm. The growth of CT26, SGC790 or NCI-H209 cells in vitro was obviously inhibited. FA-ETP-NLCs also displayed the best antitumor activity than other formulations in vivo.
  
  
  CONCLUSIONS
  The results demonstrated that FA-ETP-NLCs were efficient in selective delivery to CT26, SGC790 or NCI-H209 cells overexpressing the FA receptors. Also, FA-ETP-NLCs can sufficiently transfer ETP to the cancer cells, enhance the antitumor capacity. Thus, FA-ETP-NLCs could prove to be a superior nanomedicine to achieve tumor therapeutic efficacy.
authors.affiliation: a Department of Pharmacy, Linyi People's Hospital , Linyi , China .
authors.forename: Shumei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: b Department of Pharmacy, Linyi Cancer Hospital , Linyi , China .
authors.forename: Caixia
authors.initials: C
authors.lastname: Lu
authors.affiliation: c Department of Pharmacy, People's Hospital of Yishui County , Linyi , China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacy, Linyi People's Hospital , Linyi , China .
authors.forename: Junsheng
authors.initials: J
authors.lastname: Li
authors.affiliation: a Department of Pharmacy, Linyi People's Hospital , Linyi , China .
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D005047:Etoposide / Q000008:administration & dosage* / Q000737:chemistry*; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D050997:Nanomedicine; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D010714:Phosphatidylethanolamines; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D005047:Etoposide; D005492:Folic Acid
keywords: Box–Behnken design; etoposide; folic acid; nanostructured lipid carriers; tumor target