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This review summarizes MTX nano-delivery strategies for breast cancer, including gold, mesoporous silica, lipid–polymer hybrids, chitosan, magnetic alginate, iron oxide magnetic nanoparticles, and carbon nanotubes, focusing on sustained release and reduced toxicity through targeted delivery. Preclinical evidence supports improved outcomes, while additional clinical-trial and combination-therapy research is needed.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/advances-in-methotrexate-nano-formulations-to-enhance-therapeutic-efficacy-against-drug-resistant-breast-cancer-review/353972/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/advances-in-methotrexate-nano-formulations-to-enhance-therapeutic-efficacy-against-drug-resistant-breast-cancer-review/353972.png","ImageObject",300,407,{"name":92,"@type":93},"Sophia Brooks","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is conventional methotrexate limited in breast cancer therapy?","Question",{"text":112,"@type":113},"Conventional MTX is constrained by intestinal mucositis, high systemic toxicity, low bioavailability, poor pharmacokinetics, and a short half-life.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What types of methotrexate nano-delivery systems are reviewed for breast cancer?",{"text":117,"@type":113},"The review covers several MTX-based nanocarriers, including gold nanoparticles, mesoporous silica nanoparticles, lipid–polymer hybrid nanoparticles, chitosan nanoparticles, magnetic alginate nanoparticles, iron oxide magnetic nanoparticles, and carbon nanotubes.",{"name":119,"@type":110,"acceptedAnswer":120},"How do these nanocarriers help overcome drug resistance?",{"text":121,"@type":113},"Targeted nano-delivery approaches are described as reducing systemic toxicity and improving therapeutic outcomes in breast cancer models; the review also addresses chemoresistance mechanisms linked to drug efflux transporters like P-glycoprotein, MRP, and BCRP.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},353972,1790211967,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962084925636,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Tripathy et al. Discover Nano (2026) 21:96 [https://doi.org/10.1186/s11671-026-04520-x](https://doi.org/10.1186/s11671-026-04520-x)  \nDiscover Nano  \nREVIEW Open Access  \nAdvances in methotrexate nano-formulations  to enhance therapeutic efficacy against drugresistant breast cancer  \nSatyajit Tripathy1†, Barsha Dassarma 1†, Bhavna Jha2, Mohd Ashif Azad2, Ishita Saha3, Pragati Gupta2, Devlina Das Pramanik2, Kunzang Chosdol4 and Arindam Pramanik2,5*  \n†Satyajit Tripathy and Barsha Dassarma contributed equally to this work.  \n*Correspondence:  \nArindam Pramanik[arindampramanik87@gmail.com](arindampramanik87@gmail.com); a. [pramanik@leeds.ac.uk](pramanik@leeds.ac.uk)  \n1Amity Institute of Health Allied Science, Amity University, Noida, Uttar Pradesh 201301, India 2Amity Institute of Biotechnology, Amity University, Noida,  \nUttar Pradesh 201301, India 3Mayo Clinic Florida, 4500 San Pablo Rd S, Jacksonville, Fl 32224-1865, USA 4Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India 5School of Medicine, University of Leeds, Leeds LS97TF, UK  \nAbstract  \nMethotrexate (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 polymerbased 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.  \nKeywords Methotrexate, Breast cancer, Nano-delivery systems, Methotrexate nanoconjugate, Multidrug resistance  \n1 Introduction  \nChemotherapy remains one of the most commonly used treatment strategies for breast cancer and may be administered either before surgery (neoadjuvant) to reduce tumor burden or after surgery (adjuvant) to eradicate residual malignant cells [1]. Most conventional chemotherapeutic agents used in breast cancer require repeated intravenous administration at intervals of 2–3 weeks [1]. However, due to their nonspecific mechanism of action, these drugs often induce multiple adverse effects. Patients frequently experience toxicity-related complications such as numbness, pain, burning or tingling sensations, altered sensitivity to temperature, and generalized weakness. In addition, several chemotherapeutic agents are associated with risks of cardiotoxicity,  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted ","cbCaifQ12mcWihnB","https://ap.wps.com/l/cbCaifQ12mcWihnB","pdf",1706225,28,"English","# Abstract\n# 1 Introduction","[{\"question\":\"Why is conventional methotrexate limited in breast cancer therapy?\",\"answer\":\"Conventional MTX is constrained by intestinal mucositis, high systemic toxicity, low bioavailability, poor pharmacokinetics, and a short half-life.\"},{\"question\":\"What types of methotrexate nano-delivery systems are reviewed for breast cancer?\",\"answer\":\"The review covers several MTX-based nanocarriers, including gold nanoparticles, mesoporous silica nanoparticles, lipid–polymer hybrid nanoparticles, chitosan nanoparticles, magnetic alginate nanoparticles, iron oxide magnetic nanoparticles, and carbon nanotubes.\"},{\"question\":\"How do these nanocarriers help overcome drug resistance?\",\"answer\":\"Targeted nano-delivery approaches are described as reducing systemic toxicity and improving therapeutic outcomes in breast cancer models; the review also addresses chemoresistance mechanisms linked to drug efflux transporters like P-glycoprotein, MRP, and BCRP.\"}]","Advances in methotrexate nano-formulations to enhance therapeutic efficacy against drug-resistant breast cancer - review | PDF",1790108282,71]