title: Self-assembling peptide-based nanoparticles enhance cellular delivery of the hydrophobic anticancer drug ellipticine through caveolae-dependent endocytosis.
abstract: A special class of self-assembling peptide (EAK16-II) has been found to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, the mechanism of such peptide-EPT complexes to enhance cellular delivery and anticancer activity was evaluated. Results revealed that EAK16-II can form nanoparticles with EPT, having an average size of ∼100 nm. This nanoformulation had cytotoxicity to human lung carcinoma A549 cells that was comparable to EPT dissolved in dimethyl sulfoxide. It enhanced EPT uptake drastically when compared to the microformulation. Such enhanced uptake was significantly reduced by inhibitors specifically for the caveolae-dependent pathway. We also found both protonated and neutral forms of EPT present in the cells. Interestingly, both were found in the cytoplasm, co-localized with LysoTracker, whereas only protonated EPT was seen in the nucleus. The promising therapeutic efficacy, specific delivery pathway, and intracellular distribution pattern discovered in this work may help further develop EPT as a nanoformulation for clinical applications.
  
  
  BACKGROUND
  A special class of self-assembling peptide (EAK16-II) has been found to stabilize ellipticine in aqueous solution. The authors demonstrate therapeutic efficacy, describe specific delivery pathways, and effective intracellular distribution pattern, which will aid the development of this technology for future clinical applications.
authors: Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Research Institute, Toronto, Ontario, Canada.
authors: Roli
authors: R
authors: Bawa
authors: Shan-Yu
authors: SY
authors: Fung
authors: Atsushi
authors: A
authors: Shiozaki
authors: Hong
authors: H
authors: Yang
authors: Gang
authors: G
authors: Zheng
authors: Shaf
authors: S
authors: Keshavjee
authors: Mingyao
authors: M
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D021941:Caveolae / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D004611:Ellipticines / Q000008:administration & dosage / Q000737:chemistry; D004705:Endocytosis; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000970:Antineoplastic Agents; C098329:EAK16 peptide; D004611:Ellipticines; D009842:Oligopeptides; C034192:ellipticine