Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate...

Area of Science:

• Nanomedicine
• Drug Delivery
• Cancer Therapeutics

Background:

• Nanoparticles offer controlled drug release and targeted delivery for enhanced therapeutic efficacy.
• Quercetin, a natural compound, possesses anticancer properties but requires efficient delivery systems.
• Prostate cancer exhibits heterogeneity in receptor expression, necessitating targeted treatment strategies.

Purpose of the Study:

• To develop and optimize quercetin-loaded PLGA nanoparticles coated with chitosan and folic acid.
• To evaluate the impact of folic acid targeting on cellular uptake and cytotoxicity in prostate cancer cells (LnCap and PC-3).
• To investigate the role of Prostate-Specific Membrane Antigen (PSMA) in the targeted delivery mechanism.

Main Methods:

• Preparation and optimization of PLGA nanoparticles using a design of experiments approach.
• In vitro assessment of quercetin release kinetics (pH-dependent).
• Comparative analysis of cellular uptake and cytotoxicity assays on PSMA-high (LnCap) and PSMA-low (PC-3) prostate cancer cells.

Main Results:

• Optimized nanoparticles demonstrated sustained, pH-dependent quercetin release.
• Targeted nanoparticles exhibited significantly higher cellular uptake and cytotoxicity in LnCap cells compared to non-targeted ones.
• No significant difference in uptake or cytotoxicity was observed in PC-3 cells, confirming PSMA-specific targeting.

Conclusions:

• Folic acid-functionalized nanoparticles effectively target PSMA-expressing prostate cancer cells.
• The developed nano-system facilitates targeted delivery and release of quercetin, enhancing anti-cancer effects.
• This nanocarrier holds promise for targeted chemotherapy in prostate cancer treatment.