Christopher H Stuart1,2, Ravi Singh1,3, Thomas L Smith4, Ralph D'Agostino3,5, David Caudell6, K C Balaji1,3,7,8, William H Gmeiner1,2,3. 1. Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 2. Department of Molecular Medicine & Translation Science, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 3. Comprehensive Cancer Center at Wake Forest University, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 4. Department of Orthopedics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 5. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 6. Department of Pathology & Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 7. Department of Urology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. 8. Wake Forest Institute of Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Abstract
AIM: 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). MATERIALS & METHODS: 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. RESULTS & CONCLUSION: 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.
AIM: 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). MATERIALS & METHODS: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. RESULTS & CONCLUSION: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 humanprostate cancer xenograft model.
Entities:
Keywords:
aptamer; liposome; prostate cancer; targeted drug delivery; zinc
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