Bioengineered Liposomal Platform for Bone Metastatic Prostate Cancer

Purpose: Despite the success in treating early-stage prostate cancer (PCa), the outcomes for metastatic disease are far from ideal. Once cancer reaches distant sites, the five-year overall survival rate drops to 28%. For 90% of patients with advanced PCa, skeletal metastasis is the primary destination. To address the unmet medical need of bone-metastatic prostate cancer, we have engineered a liposomal platform to deliver a chemotherapeutic directly to the bone. Methods: First, a bone-targeting moiety with a high affinity for calcium of the hydroxyapatite in bone was conjugated to one of the lipids and characterized using H NMR, P NMR, and FTIR. Next, we incorporated the conjugate and a chemotherapeutic cargo into the liposome using a microfluidic, nanoprecipitation method. We characterized our nanoparticles using dynamic light scattering, transmission electron microscopy, and nanotracking analysis. Results : Our average nanoparticle size was 150 nm ± 2.50 with a polydispersity index (PDI) of less than 0.2 ± 0.22 and a zeta potential of 28.18 ± 1.71. Drug loading and encapsulation efficiency will be determined using LC/MS. Other characterization includes in vitro uptake studies, cytotoxicity studies in C4-2B and mPC3 cell lines, and in vivo biodistribution studies. Conclusions: We hypothesize that our liposome will ameliorate bone damage caused by metastatic PCa, inhibit PCa differentiation and proliferation, and stimulate apoptosis of PCa cells. Our overall objective is to improve the quality of life by reducing off-target side-effects and extend the overall survival rate of bone-metastatic prostate cancer patients.