Design and synthesis of folic acid conjugated chitosan-PEG nanoparticles for targeted drug delivery of sodium butyrate to prostate cancer cells

Design and synthesis of folic acid conjugated chitosan-PEG nanoparticles for targeted drug delivery of sodium butyrate to prostate cancer cells
Ali Zaman Vaziri,¹ Sepideh Khaleghi,^2,*
1. Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran.
2. Department of Medical Biotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Introduction: Prostate cancer is the sixth most common cancer in the world and the second most common cancer in men. Sodium butyrate, a histone deacetylase inhibitor, is a promising anticancer drug for many cancers. Our aim is to make folate-targeted chitosan nanoparticles containing sodium butyrate for the treatment of prostate cancer named CS-PEG-FA-SB.
Methods: In addition to the physical properties of the final nanoparticles by DLS, FTIR, TEM and SEM techniques, the toxicity of the final nanoparticles at different concentrations of the drug will be evaluated by MTT method. Furthermore, the expression of genes involved in autophagy and apoptosis in prostate cancer cell lines (PC3 and DU145) and comparison with Folate receptor negative cell line (PC3) and normal cell line (HFF-1). After treatment with chitosan nanoparticles targeted with folic acid and containing chemotherapeutic drug sodium butyrate, the apoptotic and autophagy genes were assessed by Quantitative Real time PCR method. The functional analysis of nanoparticles was examined by Apoptosis and cell cycle arrest flowcytometery analysis. Finally, the results will be evaluated with SPSS software and t-test and one-way ANOVA.
Results: Cells treated with folic acid-targeted chitosan nanoparticles containing sodium butyrate chemotherapy showed significant and dose-dependent differences at different times. The lethality of this drug nano system in PC3, DU145 and HFF-1 cells was demonstrated using MTT assay. The results of morphological study showed that chitosan nanoparticles targeted with folic acid and containing sodium butyrate chemotherapy (CS-PEG-FA-SB) have a suitable size 100±20 nm with spherical appearance. The Real Time PCR analysis showed the significant expression of apoptotic and autophagy genes in DU145 cell line treated by CS-PEG-FA-SB. The apoptosis and cell cycle arrest analysis confirmed the significant effect of CS-PEG-FA-SB treated DU145 cell line in compare with treated PC3 and HFF_1 cell lines.
Conclusion: Folic acid-targeted chitosan nanoparticles containing sodium butyrate chemotherapy drug can inhibit growth in DU145 cell line in compare with PC3 and HFF-1 cell lines, which may induce cell death by increasing the expression of apoptotic and autophagic genes. These findings could open up effective insights into prostate cancer treatment strategies.
Keywords: Prostate cancer, Apoptosis, Autophagy, Chitosan nanoparticles, Sodium butyrate, Folic acid