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.
Nanomedicine (London, England). 2016 Apr 14 [Epub ahead of print]
Christopher H Stuart, Ravi Singh, Thomas L Smith, Ralph D'Agostino, David Caudell, K C Balaji, William H Gmeiner
Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA., Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA., Department of Orthopedics, 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 Pathology & Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA., Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA., Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.