Prostate-Specific Membrane Antigen-Targeted Liposomes Specifically Deliver The Zn2+ Chelator Tpen Inducing Oxidative Stress In Prostate Cancer Cells

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.