Targeted delivery of L-Asparaginase II into ALL cells using chitosan based nanoparticles and studying the expression of apoptosis-related genes

Background and Aim: Acute Lymphoblastic Leukemia (ALL) is a type of Leukemic malignancies mostly prevalent in children between ۲ and ۱۰ years. Clinical administrations of L-asparaginase for treatment of leukemia confront some restrictions, because of its side effects and cytoplasmic toxicities. Current research, utilizing the potential of nanoparticles in stabilization and improvement of chemotherapy drugs, focuses on development and evaluation of Chitosan-based nanoparticles, and stabilization of anti-cancer drug L-asparaginase in order to effective drug delivery to cancerous cells and dominance against side effects of free drug.Methods: In order to evaluate the effectiveness of nanoparticles at cellular level, we used the culture of Acute Lymphoblastic Leukemia cells in cancerous cell line Molt-۴. Afterwards, we investigated the toxicity of nanoparticles using MTT assay. Molt-۴ cells were exposed to ۶.۲۵, ۱۲.۵, ۲۵ µg/ml of nanodrug for ۲۴, ۴۸, ۷۲ hours. Apoptotic property of synthesized nanoparticles evaluated by quantitative gene expression analysis of apoptotic genes Bax and Bcl۲, and Real-time PCR.Results: Gene expression level for Bcl۲ and Bax genes in Molt-۴ cells treated with Asparaginase was ۰.۶۱ and ۱.۵۲ respectively; and for Molt-۴ cells treated with Asparaginase-loaded nanoparticles, the gene expression level was ۰.۱۳ for Bcl۲ and ۲.۴۸ for Bax.Conclusion: MTT assay results approved cytotoxicity of nanoparticles in cancerous cell line Molt-۴. And evaluation of apoptotic gene expression indicated an increase in pro-apoptotic gene Bax expression, and decrease in anti-apoptotic gene Bcl۲ expression in samples affected by Nano drugs compared to free drug.

کلیدواژه ها:

enzyme immobilization ، targeted drug delivery ، chemotherapy ، polymeric nanocarrier