Engineering a Nanotherapeutic for Metastatic Prostate Cancer with Bone-targeting Specificity




Desai, Priyanka
Ranjan, Amalendu
Vishwanatha, Jamboor


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Prostate cancer (PCA) derived bone metastases account for 90% of metastatic tumors with a five-year overall survival rate of 29.5%. Our objective is to develop a clinically feasible nano-delivery system targeting bone-metastatic sites to prolong overall survival and improve quality of life. The purpose of this project is to engineer a cabazitaxel-loaded, poly-lactic(co-glycolic) acid (PLGA) nanoparticle (NP) with alendronate (ALN) coating to target and treat metastatic bone lesions. We hypothesize that a bone targeted nano-delivery system will ameliorate bone lesions and trigger tumor cell apoptosis. Methods: NPs were formulated using a water-in-oil-in solvent evaporation method. NPs were prepared by sonicating 50 mg/ml PLGA in dichloromethane (DCM), 5% polyvinyl alcohol (PVA), and Bis(sulfosuccinimydyl)suberate (BS3) linker. Later, ALN was conjugated to the NP. Results: Our average NP size was around 200 nm in diameter with a Zeta Potential (ZP) of – 28 mV. Our drug loading capacity (DL) was 12.4% and encapsulation efficiency was 25.3%. The IC50 value is 10 μM. NPs have also shown to be easily taken up by cancer cells. Conclusion: We have shown that our PLGA NPs have an optimal size, PDI, ZP, DL%, and EE%, which indicates that we have developed a NP that will function as a nanotherapeutic for bone metastatic PCa. The next steps will include spheroid cultures and in vivo studies.