Advances in methotrexate nano-formulations to enhance therapeutic efficacy against drug-resistant breast cancer.

Methotrexate (MTX), a widely used chemotherapeutic agent and folate antagonist, is commonly employed in the treatment of various cancers and immune-mediated inflammatory diseases. However, conventional MTX therapy is associated with several limitations, including intestinal mucositis, high systemic toxicity, low bioavailability, poor pharmacokinetics, and a short half-life. To overcome these drawbacks, recent advances have focused on encapsulating MTX within nanoparticles (NPs) or polymer-based systems, which enhance sustained drug release, reduce toxicity and improve therapeutic efficacy. This review highlights various MTX-based nano-delivery systems developed for breast cancer treatment, including gold NPs, mesoporous silica NPs, lipid–polymer hybrid NPs, chitosan NPs, magnetic alginate NPs, iron oxide magnetic NPs, and carbon nanotubes. Preclinical studies on targeted delivery approach utilizing these nanocarriers has demonstrated reduced systemic toxicity and improved treatment outcomes in breast cancer models. This highlights the need for more research focused on clinical trials and combination therapies to further enhance therapeutic benefits.