Bone Targeted Polymeric Nanoparticles for Metastatic Prostate Cancer

Purpose: Bone is the most frequent site of metastasis in several types of cancers including breast, prostate, and lung. The majority of patients that develop bone metastasis will experience complications that include pathological fractures and severe bone pain. Current treatment options for bone metastasis often cause many serious off target side effects and are ineffective. We hypothesize that delivery of cabazitaxel encapsulated bone-targeted biodegradable nanoparticles is an effective therapy for bone metastatic prostate cancer. Materials & Methods: Bone targeted nanoparticles were made using a modified water in oil in water double emulsion solvent evaporation technique. Cabazitaxel was encapsulated within PLGA nanoparticles and alendronate was used to coat the nanoparticles. Nanoparticles were characterized with mass spectroscopy, fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and dynamic light scattering (DLS). Functionally, the nanoparticles were tested in 3D prostate tumor spheroids and ex vivo bone affinity experiments. Results: Successful encapsulation of cabazitaxel within poly (lactic-co-glycolic acid) (PLGA) nanoparticles yielded an encapsulation efficiency of 58% and a drug loading of 3.74%. Release kinetics demonstrated a controlled release of the drug with 60% of cabazitaxel released at 1 hour and 98% at 72 hours. Surface characterization with FTIR confirmed alendronate attachment to the surface of the nanoparticle. SEM and DLS showed an acceptable degree of size dispersity with spherical nanoparticles. Targeted nanoparticles had a 4-fold increased affinity to bone compared to non-targeted nanoparticles at 6 hours and a 8-fold increased affinity to bone at 72 hours in bone affinity experiments. 3D tumor spheroid assay indicated that spheroids treated with equivalent doses of free drug and drug loaded nanoparticles resulted in similar cytotoxic performance. Conclusion: We have engineered bone targeted PLGA nanoparticles for treating metastatic prostate cancer. Future studies will assess the in vivo bone targeting capabilities of the nanoparticles as well as therapeutic effects in an intraosseous tumor model.