title: Prostate-specific membrane antigen-targeted liposomes specifically deliver the Zn(2+) chelator TPEN inducing oxidative stress in prostate cancer cells.
abstract: To evaluate the potential use of zinc chelation for prostate cancer therapy using a new liposomal formulation of the zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN).
  
  
  
  TPEN was encapsulated in nontargeted liposomes or liposomes displaying an aptamer to target prostate cancer cells overexpression prostate-specific membrane antigen. The prostate cancer selectivity and therapeutic efficacy of liposomal (targeted and nontargeted) and free TPEN were evaluated in vitro and in tumor-bearing mice.
  
  
  
  TPEN chelates zinc and results in reactive oxygen species imbalance leading to cell death. Delivery of TPEN using aptamer-targeted liposomes results in specific delivery to targeted cells. In vivo experiments show that TPEN-loaded, aptamer-targeted liposomes reduce tumor growth in a human prostate cancer xenograft model.
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Molecular Medicine & Translation Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Stuart
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Comprehensive Cancer Center at Wake Forest University, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Singh
authors.affiliation: Department of Orthopedics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Smith
authors.affiliation: Comprehensive Cancer Center at Wake Forest University, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.affiliation: Department of Pathology & Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: David
authors.initials: D
authors.lastname: Caudell
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Comprehensive Cancer Center at Wake Forest University, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Urology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: K C
authors.initials: KC
authors.lastname: Balaji
authors.affiliation: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Department of Molecular Medicine & Translation Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.|Comprehensive Cancer Center at Wake Forest University, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Gmeiner
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D052157:Aptamers, Nucleotide / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005029:Ethylenediamines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015032:Zinc / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D052157:Aptamers, Nucleotide; D002614:Chelating Agents; D005029:Ethylenediamines; D008081:Liposomes; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
keywords: aptamer; liposome; prostate cancer; targeted drug delivery; zinc