One of the main drivers of mortality for men suffering from prostate cancer (PCa) are bone metastases. Advanced prostate cancer is known for it’s affinity for metastasizing to bone, making this an attractive therapeutic target. In addition to chemotherapeutics, men afflicted by PCa are given specific treatment for bone metastasis. Bisphosphonates have shown healing of metastatic lesions when administered to patients. Here we use pamidronate as the bisphosphonate which will be modified to be encapsulated in our PCa targeting polymeric nanoparticle (NP). NP mediated delivery of the prodrug in conjunction with a previously reported chemotherapeutic and anti-inflammatory prodrug will greatly increase the effectiveness of the NPs to reduce tumor burden while also preventing metastases. Pamidronate prodrug was synthesized to ensure encapsulation of the highly hydrophilic drug. The prodrug loaded NPs were evaluated for their principle parameters such as size, zeta potential, drug release profile, drug loading and effective dosage. The efficacy of the NP to reduce the pro-migratory and pro-invasive characteristics of prostate cancer cells were evaluated<i>.</i>The pamidronate prodrug was found to load effectively into the polymeric nanoparticles using the nanoprecipitation method. These were then administered in <i>in vitro </i>studies which show a reduction in the ability of the PCa cells to migrate and invade when compared to untreated controls. The NPs also showed the ability to inhibit osteoclastogenesis which is needed for the cells to form bone tumors. C4-2b metastatic prostate cancer cells were tagged with luciferase and used to evaluate the ability of the NP to prevent bone metastases. This nanoparticle platform can lead to an effective treatment plan for primary prostate cancer while at the same time preventing the potential for metastasis.

Combination nanoparticle platform for the treatment of metastatic prostate cancer

ACS Spring Meeting 2021

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