title: Conveying a newly designed hydrophilic anti-human thymidylate synthase peptide to cisplatin resistant cancer cells: are pH-sensitive liposomes more effective than conventional ones?
abstract: BACKGROUND
  LR-peptide, a novel hydrophilic peptide synthetized and characterized in previous work, is able to reduce the multi-drug resistance response in cisplatin (cDPP) resistant cancer cells by inhibiting human thymidylate synthase (hTS) overexpressed in several tumors, including ovarian and colon-rectal cancers, but it is unable to enter the cells spontaneously.
  
  
  OBJECTIVE
  The aim of this work was to design and characterize liposomal vesicles as drug delivery systems for the LR peptide, evaluating the possible benefits of the pH-responsive feature in improving intracellular delivery.
  
  
  METHODS
  For this purpose, conventional and pH-sensitive liposomes were formulated, compared regarding their physical-chemical properties (size, PDI, morphology, in vitro stability and drug release) and studied for in vitro cytotoxicity against a cDDP-resistant cancer cells.
  
  
  CONCLUSIONS
  Results indicated that LR peptide was successfully encapsulated in both liposomal formulations but at short incubation time only LR loaded pH-sensitive liposomes showed cell inhibition activity while for long incubation time the two kinds of liposomes demonstrated the same efficacy.
  
  
  CONCLUSIONS
  Data provide evidence that acidic pH-triggered liposomal delivery is able to significantly reduce the time required by the systems to deliver the drug to the cells without inducing an enhancement of the efficacy of the drug.
authors.affiliation: a Department of Life Sciences , University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sacchetti
authors.affiliation: b Department of Biomedical , Metabolical and Neural Sciences, University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Arca
authors.affiliation: c Centro Interdipartimentale Grandi Strumenti (CIGS) , University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Genovese
authors.affiliation: d Department of Pharmaceutical Sciences , University of Ferrara , Ferrara , 44100 , Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pacifico
authors.affiliation: a Department of Life Sciences , University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Maretti
authors.affiliation: e Department of Engineering Enzo Ferrari , University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hanuskova
authors.affiliation: a Department of Life Sciences , University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Iannuccelli
authors.affiliation: a Department of Life Sciences , University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Costi
authors.affiliation: a Department of Life Sciences , University of Modena and Reggio Emilia , Modena , Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Leo
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D008081:Liposomes; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D013940:Thymidylate Synthase; D002945:Cisplatin
keywords: Hydrophilic peptide; cancer cells; endosomal escape; human thymidylate synthase; pH sensitive liposomes