title: Cytotoxic enhancement of hexapeptide-conjugated micelles in EGFR high-expressed cancer cells.
abstract: OBJECTIVE
  The aim of this study was to develop the hexapeptide-conjugated active targeting micelles for delivery of doxorubicin (DOX) and paclitaxel (PTX) to EGFR high-expressed cancer cells.
  
  
  METHODS
  A hexapeptide, which mimicked the EGFR, was applied as a targeting ligand. The active targeting micelles were prepared using the synthesized poly(D,L-lactide-co-glycolide)-PEG copolymer conjugated with the hexapeptide. The micelles were used for encapsulating DOX and/or PTX, and the cellular uptake, in vitro drug release and cellular viability of drug-loaded peptide-conjugated and peptide-free micelles were investigated.
  
  
  RESULTS
  The particle size of drug-loaded peptide-conjugated and peptide-free micelles was < 150 nm with narrow size distribution. The uptake of peptide-conjugated micelles was more efficient in EGFR high-expressed MDA-MB-468 and SKOV3 cells than in EGFR low-expressed HepG2 cells. The in vitro release of DOX and PTX was faster in pH 4.0 (500 U lipase) than in pH 7.4 release medium. The cytotoxicity in terms of IC50 of DOX/PTX-loaded peptide-conjugated micelles was 4.8-folds lower than that of peptide-free micelles and 18.2-folds lower than DOX/PTX drug solution in SOKV3 cells.
  
  
  CONCLUSIONS
  The peptide-conjugated micelles acted as a nanocarrier to increase intracellular accumulation of anticancer drugs in EGFR high-expressed SKOV3 cancer cells to enhance cell cytotoxicity.
authors.affiliation: National Taiwan University, Graduate Institute of Pharmaceutical Sciences, School of Pharmacy , No. 33 Lin San S. Rd, Taipei 100 , Taiwan +886 2 33668765 ; +886 2 23916126 ; wjlin@ntu.edu.tw.
authors.forename: Wen Jen
authors.initials: WJ
authors.lastname: Lin
authors.forename: Li Ting
authors.initials: LT
authors.lastname: Kao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017239:Paclitaxel
keywords: EGFR; doxorubicin; hexapeptide; micelles; paclitaxel