title: Attenuation of nontargeted cell-kill using a high-density lipoprotein-mimicking peptide--phospholipid nanoscaffold.
abstract: Research in the development of nanoscale drug carriers primarily focuses on maximizing drug delivery efficiency to tumor tissues. However, less attention has been given to minimizing drug toxicity to non-targeted cells to enhance therapeutic selectivity.
  
  
  OBJECTIVE
  Herein, we report on the use of a newly developed high-density lipoprotein-mimicking peptide-phospholipid nanoscaffold (HPPS) to deliver a lipophilic drug, paclitaxel oleate (PTXOL).
  
  
  RESULTS
  The formulated PTXOL HPPS (120:1) drastically increased therapeutic selectivity by reducing cytotoxicity of PTXOL to nontargeted cells. Using mice bearing targeted (KB) and nontargeted (HT1080) tumors as models, we demonstrated that tumor volume of nontargeted cells was decreased to 57% by PTXOL treatment but increased to 1220% by PTXOL HPPS treatment. However, upon treatment of paclitaxel, PTXOL and PTXOL HPPS, tumor volumes of targeted groups were reduced to 85, 50 and 63%, respectively.
  
  
  CONCLUSIONS
  These data strongly suggest that HPPS can attenuate toxicity of anticancer drugs to nontargeted cells, resulting in cell-killing efficacy only on targeted cells.
authors: Campbell Family Cancer Research Institute and Ontario Cancer Institute, University Health Network, Toronto, Canada.
authors: Mi
authors: M
authors: Yang
authors: Juan
authors: J
authors: Chen
authors: Weiguo
authors: W
authors: Cao
authors: Lili
authors: L
authors: Ding
authors: Kenneth K
authors: KK
authors: Ng
authors: Honglin
authors: H
authors: Jin
authors: Zhihong
authors: Z
authors: Zhang
authors: Gang
authors: G
authors: Zheng
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008075:Lipoproteins, HDL; D010455:Peptides; D010743:Phospholipids; D017239:Paclitaxel