• Therapeutic effects of methotrexate-loaded chitosan nanoparticles on breast cancer: a review
  • Iliya Ahmadzadeh kermani,1 Elahe Kamelnia,2,* Reyhane Kamelnia,3
    1. Islamic Azad University, Mashhad Branch
    2. Department of biology, Faculty of sciences, Mashhad branch, Islamic Azad University, Mashhad, Iran
    3. Faculty of Medicine, Mashhad University of Azad Medical Sciences, Mashhad, Iran


  • Introduction: Breast cancer is the most commonly diagnosed cancer among women, accounting for 11.7% of all cancer cases globally. According to the World Health Organization, in 2022, 2.3 million women worldwide were diagnosed with breast cancer. Women in every country are susceptible to breast cancer after puberty, with a higher prevalence observed in older age groups. Primary treatment modalities for breast cancer include chemotherapy, radiotherapy, and surgery, but their effectiveness remains limited. Chitosan (CS) and methotrexate (MTX) represent an advanced drug delivery system in the fight against cancer. It is a biodegradable and non-toxic polymer with strong biocompatibility, minimal immune response, mucoadhesive properties, and absorption-enhancing capabilitie. So it can be utilized in various ways to deposit MTX within cancer cells. Furthermore, CS can be coated with hyaluronic acid or folic acid to enable active targeting of cancer cells. Notably, CS and MTX bridge the gap between conventional chemotherapeutic drugs and novel drug delivery systems.
  • Methods: Methotrexate (MTX) is used for treating various cancers, including breast cancer. Its mechanism of action involves indirect inhibition of cell division by targeting enzymes related to folate metabolism, especially dihydrofolate reductase (DHFR). MTX exerts its anticancer effects by inhibiting DHFR, leading to depletion of intracellular tetrahydrofolate (THF) pools essential for thymidylate and purine synthesis. Folates are critical cofactors for DNA and RNA synthesis; thus, the absence of thymidine or purines prevents DNA and RNA biosynthesis. Loading MTX into CS nanoparticles (CSNPs) enhances MTX cellular targeting via receptor-mediated folate endocytosis, thereby improving MTX delivery and efficacy. Additionally, MTX is released into the cytoplasm through binding to DHFR, resulting in DNA synthesis blockade and induction of apoptosis.
  • Results: Nanoparticle-based drug delivery systems offer numerous advantages, including targeted delivery to cancer cells, minimization of off-target effects, enhanced drug stability and solubility, controlled release, and improved therapeutic efficacy. Polymer-based nanocarriers such as CS can increase the biological half-life of drugs, reduce side effects, improve solubility, and decrease dosing frequency. So these polymers can be A worthy choice in drug delivery systems.
  • Conclusion: Chitosan nanoparticles developed as carriers exhibited maximum encapsulation efficiency for hydrophilic MTX. Meanwhile, MTX-loaded nanoparticles were evaluated for their anticancer efficacy. Chitosan nanoparticles loaded with methotrexate represent an effective approach in breast cancer treatment. These nanoparticles displayed favorable physicochemical properties, including appropriate size, positive surface charge, and high encapsulation efficiency. Methotrexate-loaded chitosan nanoparticles reduced breast cancer cell viability at low doses. Their small size makes these encapsulated nanoparticles an effective and novel technology for breast cancer treatment. Continued research in this field is hoped to improve breast cancer treatment outcomes and reduce reliance on other therapeutic methods.
  • Keywords: Nanoparticles, Chitosan, Breast cancer, Methotrexate