title: Curcumin-loaded nanoliposomes linked to homing peptides for integrin targeting and neuropilin-1-mediated internalization.
abstract: BACKGROUND
  Curcumin, a naturally occurring polyphenol, has been extensively studied for its broad-spectrum anticancer effects. The potential benefits are, however, limited due to its poor water solubility and rapid degradation which result in low bioavailability on administration.
  
  
  OBJECTIVE
  This study encapsulates curcumin in nanoliposomes including an integrin-homing peptide combined with a C end R neuropilin-1 targeting motif for targeted delivery and receptor-mediated internalization, respectively.
  
  
  METHODS
  The linear GHHNGR (Glycine-Histidine-Histidine-Asparagine-Glycine-Arginine) was synthesized through F-moc chemistry on 2-chlorotrityl chloride resin and conjugated to oleic acid. The lipoyl-peptide units were then co-assembled with lecithin and 0-75 mole % Tween-80 into liposomes. Curcumin was passively entrapped using a film hydration technique and its degradation profile was examined within seven consecutive days. The cytotoxic effects of the curcumin-loaded liposomes were studied on MCF-7 and MDA-MB-468, during 24 h exposure in MTT assay.
  
  
  RESULTS
  The maximum curcumin entrapment (15.5% W/W) and minimum degradation (< 23%) were obtained in a pH switch loading method from 5.7 to 8, in nanoliposomes (< 50 nm) containing oleyl-peptide, lecithin and Tween-80 (1:1:0.75 mole ratio). The oleyl-peptide did not prove any haemolytic activity (< 1.5%) up to 10-fold of its experimental concentration. The curcumin-loaded liposomes displayed significant reduction in the viabilities of MCF-7 (IC503.8 μM) and MDA-MB-468 (IC505.4 μM).
  
  
  CONCLUSIONS
  This study indicated potential advantages of the peptide-conjugated liposomes in drug transport to the cancer cells. This feature might be an outcome of probable interactions between the targeted nanoliposomes with the integrin and neuropilin-1 receptors.
authors.affiliation: a Department of Pharmaceutical Biomaterials School of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Sogol
authors.initials: S
authors.lastname: Kangarlou
authors.affiliation: b Peptide Chemistry Research Center , K.N. Toosi University of Technology , Tehran , Iran.
authors.forename: Sorour
authors.initials: S
authors.lastname: Ramezanpour
authors.affiliation: b Peptide Chemistry Research Center , K.N. Toosi University of Technology , Tehran , Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Balalaie
authors.affiliation: c Department of Medical Mycology School of Medical Sciences , Tarbiat Modares University , Tehran , Iran.
authors.forename: Shahla
authors.initials: S
authors.lastname: Roudbar Mohammadi
authors.affiliation: a Department of Pharmaceutical Biomaterials School of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.|d Medical Biomaterials Research Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Ismaeil
authors.initials: I
authors.lastname: Haririan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004705:Endocytosis; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D016023:Integrins / Q000378:metabolism*; D008081:Liposomes; D061986:MCF-7 Cells; D053758:Nanoparticles; D039942:Neuropilin-1 / Q000378:metabolism*; D019301:Oleic Acid / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D016023:Integrins; D008081:Liposomes; D009842:Oligopeptides; D039942:Neuropilin-1; D019301:Oleic Acid; D003474:Curcumin
keywords: Encapsulation; endosome escape; nanotechnology; stability