title: Targeted delivery of paclitaxel to EphA2-expressing cancer cells.
abstract: OBJECTIVE
  YSA is an EphA2-targeting peptide that effectively delivers anticancer agents to prostate cancer tumors. Here, we report on how we increased the drug-like properties of this delivery system.
  
  
  METHODS
  By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo.
  
  
  RESULTS
  dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared with vehicle or paclitaxel treatments.
  
  
  CONCLUSIONS
  This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anticancer agents to a variety of tumor types.
authors.affiliation: Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 90237, USA.
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.forename: Roberta
authors.initials: R
authors.lastname: Noberini
authors.forename: John L
authors.initials: JL
authors.lastname: Stebbins
authors.forename: Swadesh
authors.initials: S
authors.lastname: Das
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bainan
authors.initials: B
authors.lastname: Wu
authors.forename: Sayantan
authors.initials: S
authors.lastname: Mitra
authors.forename: Sandrine
authors.initials: S
authors.lastname: Billet
authors.forename: Ana
authors.initials: A
authors.lastname: Fernandez
authors.forename: Neil A
authors.initials: NA
authors.lastname: Bhowmick
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kitada
authors.forename: Elena B
authors.initials: EB
authors.lastname: Pasquale
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pellecchia
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D036104:Receptor, EphA2 / Q000235:genetics* / Q000378:metabolism; D014184:Transplantation, Homologous; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010455:Peptides; D036104:Receptor, EphA2; D017239:Paclitaxel