title: Improved therapeutic activity of HER2 Affibody-targeted cisplatin liposomes in HER2-expressing breast tumor models.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether the conjugation of anti-HER2-Affibody to cisplatin PEGylated liposome can efficiently enhance the therapeutic effectiveness of the targeted liposome.
  
  
  METHODS
  First, Affibody molecules were incubated with Mal-PEG2000-DSPE micelle to afford formation of a maleimide-mediated thioether coupling to the COOH-terminal cysteine of Affibody. Cisplatin-loaded liposomes composed of hydrogenated soy phosphatidylcholine/ cholesterol/mPEG2000-DSPE (56.5:38.5:5 molar ratio) (150 mM) were prepared and characterized by their physicochemical properties. Affibody-conjugated micelles were then transferred into preformed liposomes by means of post insertion. The cytotoxicity and cellular uptake of Affibody-targeted (affisome) and nontargeted liposomes were tested in HER2(+) SK-BR-3, and the in vivo therapeutic activity was evaluated in TUBO breast cancer models.
  
  
  RESULTS
  Anti-HER2 affisome demonstrated a higher amount of platinum intracellularly, and affected HER2(+)-SK-BR-3 cell death was at lower concentrations compared with its liposome counterparts. Further, cisplatin-affisome showed greater therapeutic efficiency than nontargeted liposome in HER2(+)-TUBO models. Equally promising, the affisome-treated mice did extend the survival of animals by several days and even left one tumor-free survivor.
  
  
  CONCLUSIONS
  Affibody-targeting endowed cisplatin liposomes with significantly enhanced, albeit modest, therapeutic activity in HER2-overexpressing tumor model; however, further values are yet to be determined to advance clinical translation of these targeted nanoparticulates.
authors.affiliation: a Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Seyedeh Hoda
authors.initials: SH
authors.lastname: Alavizadeh
authors.affiliation: b Immunogenetics Research Center, Department of Physiology and Pharmacology, Faculty of Medicine , Mazandaran University of Medical Sciences , Sari , Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Akhtari
authors.affiliation: c Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: c Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Golmohammadzadeh
authors.affiliation: a Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy , Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008081:Liposomes; D008301:Maleimides / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D002945:Cisplatin; D008081:Liposomes; D008301:Maleimides; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); C043592:maleimide
keywords: Affisome; anti-HER2 Affibody; breast cancer; cisplatin; stealth liposome