Targeted PEGylated Chitosan Nano-complex for Delivery of Sodium Butyrate to Prostate Cancer: An In Vitro Study

Abstract

Introduction: Cancer remains a challenging issue against human health throughout the world; As a result, introducing novel approaches would be beneficial for cancer treatment. In this research, sodium butyrate (Sb) is one of the effective anti-cancer therapeutics (also a potent survival factor for normal cells) that was used for prostate cancer suppression in the platform of modified chitosan (CS) nano-complex (polyethylene glycol (PEG)-folic acid (FA)-Sb-CS). Methods: Different analytical devices including Fourier transform infrared, dynamic light scattering, high-performance liquid chromatography, scanning electron microscopy, and transmission electron microscopy were applied for the characterization of synthetics. On the other hand, biomedical tests including cell viability assay, molecular and functional assay of apoptosis/autophagy pathways, and cell cycle arrest analysis were potentially implemented on human PC3 (folate receptor-negative prostate cancer) and DU145 (folate receptor-positive prostate cancer) and HFF-1 normal cell lines. Results: The quality of the syntheses was effectively verified, and the size range from 140 to 170 nm was determined for the PEG-CS-FA-Sb sample. Also, 75  ±  5% of drug entrapment efficiency with controlled drug release manner (Sb release of 54.21% and 74.04% for pHs 7.4 and 5.0) were determined for nano-complex. Based on MTT results, PEG-CS-FA-Sb has indicated 72.07% and 33.53% cell viability after 24 h of treatment with 9 mM on PC3 and DU145 cell lines, respectively, which is desirable anti-cancer performance. The apoptotic and autophagy genes overexpression was 15-fold (caspase9), 2.5-fold (BAX), 11-fold (ATG5), 2-fold (BECLIN1), and 3-fold (mTORC1) genes in DU145 cancer cells. More than 50% of cell cycle arrest and 45.05% of apoptosis were obtained for DU145 cancer cells after treatment with nano-complex. Conclusion: Hence, the synthesized Sb-loaded nano-complex could specifically suppress prostate cancer cell growth and induce apoptosis and autophagy in the molecular and cellular phases.