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Programmable nanorobots—nanoscale devices with autonomous or guided motion—can actively cross the BBB and release cytotoxic drugs at tumor sites. Biomimetic coatings, enzymatic propulsion, and pH-responsive targeting support selective accumulation while minimizing systemic toxicity. Preclinical work in China, the United States, and Europe shows progress, but clinical translation demands rigorous attention to safety, biocompatibility, and regulatory oversight.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/nanorobots-crossing-the-bloodbrain-barrier-for-targeted-chemotherapy-the-next-frontier-letter-to-the-editor/435560/",{"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/nanorobots-crossing-the-bloodbrain-barrier-for-targeted-chemotherapy-the-next-frontier-letter-to-the-editor/435560.png","ImageObject",300,407,{"name":92,"@type":93},"jayni","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is the blood–brain barrier a key obstacle in chemotherapy for glioblastoma?","Question",{"text":112,"@type":113},"The BBB prevents most systemic chemotherapeutic agents from reaching brain tumors, leading to poor tumor penetration and limited therapeutic effectiveness.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What capabilities do programmable nanorobots bring to targeted chemotherapy?",{"text":117,"@type":113},"They can sense, propel, and target, enabling active traversal of the BBB and responsive drug release triggered by tumor-specific cues such as acidic pH or enzymatic activity.",{"name":119,"@type":110,"acceptedAnswer":120},"What major barriers remain before nanorobotic chemotherapy can reach clinical use?",{"text":121,"@type":113},"Successful translation depends on safety and biocompatibility, regulatory oversight, ensuring biodegradability, avoiding immune clearance, and providing ethical transparency for AI-guided systems.","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},435560,1790763163,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":14,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":24,"preview_page_count":4},3985747859343,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Letter to the Editor  \nNanorobots crossing the blood–brain barrier for targeted chemotherapy: the next frontier  \nMuhammad Khizar, MDa , Muhammad Zaib, MDa , Raghabendra Kumar Mahato, MBBSb ,*  \nAbstract  \nThe impermeability of the blood–brain barrier (BBB) remains one of the greatest challenges in neuro-oncology, limiting the  \neffectiveness of chemotherapeutic delivery to malignant brain tumors. Programmable nanorobots, nanoscale devices with autonomous or guided motion have emerged as a transformative technology capable of actively crossing the BBB and releasing cytotoxic drugs directly at tumor sites. By integrating biomimetic coatings, enzymatic propulsion, and PH-responsive targeting, these systems achieve selective tumor accumulation while minimizing systemic toxicity. Preclinical studies from China, the United States, and Europe demonstrate significant advances in nanorobot-assisted chemotherapy, heralding a paradigm shift in glioblastoma management. Despite promising results, clinical translation requires careful attention to safety, biocompatibility, and regulatory oversight. This letter outlines current progress, key technical strategies, and future directions in nanorobotic chemotherapy. The approach holds profound implications for precision medicine and offers renewed hope for patients with intractable brain malignancies.  \nKeywords: blood–brain barrier, cancer, chemotherapy, nanorobots, oncology  \nTo the Editor,  \nGlioblastoma multiforme remains one of the most lethal cancers, with median survival under 2 years despite maximal therapy. The principal barrier to therapeutic success is the blood–brain barrier (BBB), which excludes most systemic chemotherapeutic agents[1] . Conventional drug delivery achieves poor tumor penetration, prompting an urgent need for novel, precise delivery methods.  \nNanorobots, engineered nanoscale devices combining sensing, propulsion, and targeting, offer a potential breakthrough. These intelligent systems can actively traverse the BBB, guided by magnetic or enzymatic propulsion, and release drugs in response to tumor-specific cues such as acidic pH or enzymatic activity. In China, natural killer cell membrane-coated nanorobots have been shown to transiently open endothelial junctions and deliver chemotherapeutics directly to glioma tissue[2]. In the United States, DNA-origami nanorobots capable of exposing cytotoxic ligands in acidic microenvironments demonstrated tumor-specific apoptosis and minimal off-target toxicity[3] . Similarly, enzyme-driven  \naFaculty of Medicine, Georgian American University, Tbilisi, Georgia and bDepartment of Medicine, Faculty of Medicine, Gandaki Medical College Teaching Hospital and Research Center, Pokhara, Nepal  \nSponsorships or competing interests that may be relevant to content are disclosed at the end of this article.  \n*Corresponding author. Address: Department of Medicine, Faculty of Medicine, Gandaki Medical College Teaching Hospital and Research Center, Pokhara 33700, Gandaki, Nepal. Tel.: +977-9745829807.  \nE-mail: [102raghabendrakumarmahato@gmail.com](102raghabendrakumarmahato@gmail.com) (R.K. Mahato).  \nCopyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Annals of Medicine & Surgery (2026) 88:1124–1125  \nReceived 20 November 2025; Accepted 25 November 2025  \nPublished online 6 December 2025  \n[http://dx.doi.org/10.1097/MS9.0000000000004532](http://dx.doi.org/10.1097/MS9.0000000000004532)  \nnanomotors developed in Germany and Japan enhance penetration through brain vasculature, highlighting rapid global progress[4].  \nClinically, nanorobotic delivery systems promise higher drug concentration at t","cbCaihLF5zLDrVcU","https://ap.wps.com/l/cbCaihLF5zLDrVcU","pdf",168910,"English","# Abstract\n# To the Editor\n## Background: glioblastoma and the BBB\n## Nanorobotic strategies for BBB crossing and tumor-selective drug release\n## Clinical promise and remaining challenges\n# Ethical approval and disclosures\n## Consent, funding, contributions, and conflicts of interests\n## Data availability, acknowledgements, and references","[{\"question\":\"Why is the blood–brain barrier a key obstacle in chemotherapy for glioblastoma?\",\"answer\":\"The BBB prevents most systemic chemotherapeutic agents from reaching brain tumors, leading to poor tumor penetration and limited therapeutic effectiveness.\"},{\"question\":\"What capabilities do programmable nanorobots bring to targeted chemotherapy?\",\"answer\":\"They can sense, propel, and target, enabling active traversal of the BBB and responsive drug release triggered by tumor-specific cues such as acidic pH or enzymatic activity.\"},{\"question\":\"What major barriers remain before nanorobotic chemotherapy can reach clinical use?\",\"answer\":\"Successful translation depends on safety and biocompatibility, regulatory oversight, ensuring biodegradability, avoiding immune clearance, and providing ethical transparency for AI-guided systems.\"}]","Nanorobots crossing the blood–brain barrier for targeted chemotherapy: the next frontier - Letter to the Editor | PDF",1790674167]