The synergistic anti-leishmanial effect of photodynamic therapy employing chemotherapy-mediated nanocomposites
Elahe Molaakbari, Ahmad Khosravi, Ehsan Salarkia, Iraj Sharifi, Alireza Keyhani, Mehdi Bamorovat, Mohammad Zarif, Fatemeh Sharifi
Abstract
Cutaneous leishmaniasis (CL) presents a significant therapeutic challenge due to limitations of current treatments like meglumine antimoniate (MAT), including drug resistance and adverse side effects. Photodynamic therapy (PDT) has emerged as a promising, non-invasive alternative. This study explored the synergistic potential of combining PDT with chemotherapy using novel MAT-loaded nanocomposites for enhanced anti-leishmanial activity. A novel nanocomposite, Co-Fe 2 O 4 @GO-poly(AMPS-co-AM), was synthesized and characterized using energy-dispersive X-ray spectroscopy (EDX), elemental mapping, and high-resolution transmission electron microscopy (HR-TEM). MAT was immobilized onto the nanocomposite, forming NCMAT. The in vitro anti-leishmanial efficacy of NCMAT against L. tropica was evaluated using flow cytometry, MTT assays, and real-time polymerase chain reaction (PCR) to assess gene expression. The characterization techniques confirmed the successful synthesis and MAT loading of the nanocomposite. In vitro studies demonstrated that NCMAT combined with PDT resulted in a 78% increase in hydroxyl radical production and exhibited a significant reduction (X%) in parasite viability compared to MAT alone. This enhanced activity is likely attributed to increased reactive oxygen species (ROS) production and immunomodulation. Combining nanotechnology with PDT offers a promising approach for treating CL. The Co-Fe 2 O 4 @GO-poly(AMPS-co-AM) nanocomposites demonstrated improved therapeutic outcomes in vitro. While these results are encouraging, further research is crucial to evaluate the clinical safety and efficacy of this combined therapeutic strategy.