Nano-Targeted Delivery of Toremifene, an Estrogen Receptor-α Blocker in Prostate Cancer.

Purpose: Estrogen Receptor-α (ERα) expression is increased in prostate cancer and acts as an oncogene. We propose that blocking of estrogen hormone binding to ERα using the ERα blocker toremifene will reduce the tumorigenicity of prostate cancer, and nano-targeted delivery of toremifene will improve anticancer efficacy. We report the synthesis and use in an orthotopic mouse model of PLGA-PEG nanoparticles encapsulating toremifene and nanoparticles encapsulating toremifene that are also conjugated to anti-PSMA for targeted prostate tumor delivery.

Methods: Human prostate cancer cell line PC3M and a nude mouse model were used to test efficacy of nano-targeted and nano-encapsulated toremifene versus free toremifene on the growth and differentiation of tumor cells.

Results: Treatment with free toremifene resulted in a significant reduction in growth of prostate tumor and proliferation, and its nano-targeting resulted in greater reduction of prostate tumor growth, greater toremifene tumor uptake, and enhanced tumor necrosis. Tumors from animals treated with nano-encapsulated toremifene conjugated with anti-PSMA showed about a 15-fold increase of toremifene compared to free toremifene.

Conclusions: Our data provide evidence that blocking ERα by toremifene and targeting prostate cancer tissues with anti-PSMA antibody on the nanoparticles' surface repressed the tumorigenicity of prostate cancer cells in this mouse model.