Davoud Jafari-Gharabaghlou
, Urjwan Alali, Fadhil Jawad Al-Tu’ma, Hamid Babavalian, Mozafar Mohammadi, Mohammad Sadegh Hashemzadeh
* 1 Nanobiotechnology Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
2 Department of Pharmaceutical Chemistry, College of Pharmacy, University of Kerbala, Kerbala, Iraq.
3 Medical Laboratories Techniques Department, College of Health and Medical Techniques, Al-Mustaqbal University, 51001, Babylon, Iraq.
4 Department of Chemistry and Biochemistry, College of Medicine, University of Kerbala, Kerbala, Iraq.
5 Applied Biotechnology Research Center, New Health Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Abstract
Purpose: Utilizing targeted drug delivery in oncology represents a valuable strategy to enhance the therapeutic efficacy of chemotherapy and simultaneously mitigate its adverse effects. Our present investigation focused on harnessing the therapeutic properties of melatonin as an anti-cancer agent and improving its bioavailability by employing a drug delivery system based on folic acid-decorated niosomal nanoparticles. Methods: To deliver melatonin, a niosomal and a folic acid decorated niosomal system was used. Nanoparticles were synthesized with the thin film hydration method and characterized by AFM, SEM, DLS, and FT-IR techniques. The cytotoxic effects and changes in gene expression were assessed using MTT and real-time PCR techniques, respectively. Additionally, flow cytometry experiments were conducted to investigate their impact on cell cycle arrest and apoptosis induction. Results: Nanoparticle analysis revealed that the size distribution of blank niosomes, melatonin-loaded niosomal nanoparticles, and melatonin-loaded folic acid-decorated niosomal nanoparticles were 157 ± 8.96 nm, 198 ± 12.34 nm, and 239.9 ± 39.64 nm, respectively. Controlled release studies indicated that over 96 hours, the maximum amount of melatonin released was approximately 60% at pH 7.4 and 73% at pH 5. The results demonstrated enhanced cell cytotoxicity of melatonin when encapsulated in melatonin-loaded folic acid-decorated niosomal compared to pure melatonin and niosomal nanoparticles. Furthermore, melatonin-loaded folic acid-decorated niosomal nanoparticles exhibited superior outcomes in terms of promoting apoptosis and cell cycle arrest compared to other tested substances. Conclusion: Overall, melatonin-loaded folic acid-decorated niosomal nanoparticles demonstrate a significant capability as an effective therapeutic strategy for targeting colorectal cancer cells.