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This review analyzes precision-engineered nanocarriers—lipid-, polymeric-, protein-derived, and metallic-hybrid platforms—and explains how they target multiple steps of the cancer–immunity cycle, supporting antigen presentation, T-cell activation, and cytotoxic lymphocyte infiltration. It highlights clinically approved nanoformulations and addresses remaining barriers such as nanoparticle complexity, clearance, heterogeneous biology, and toxicity, outlining future needs for integrated engineering, administration, translational validation, and rational combinations.",{"@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/nano-enabled-strategies-for-targeted-immunotherapy-in-gastrointestinal-cancers/371787/",{"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/nano-enabled-strategies-for-targeted-immunotherapy-in-gastrointestinal-cancers/371787.png","ImageObject",300,407,{"name":92,"@type":93},"Mimi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why are novel targeted immunotherapy strategies needed for gastrointestinal cancers?","Question",{"text":112,"@type":113},"GI cancers remain a major cause of cancer deaths, and existing therapies are limited by suboptimal response rates, safety concerns, and difficulties achieving sustained immune effects.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What roles do nanomedicine-based platforms play in immunotherapy within this review?",{"text":117,"@type":113},"Nanocarriers can precisely modulate tumor immune microenvironments and intervene across the cancer–immunity cycle, enabling improved antigen presentation, T-cell activation, and cytotoxic lymphocyte infiltration.",{"name":119,"@type":110,"acceptedAnswer":120},"What challenges still hinder clinical implementation of nano-enabled immunotherapies?",{"text":121,"@type":113},"Clinical translation is constrained by nanoparticle complexity, heterogeneous tumor biology, clearance mechanisms, and toxicity concerns.","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},371787,1790637593,{"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":34,"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},2336477974920,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","TYPE Review  \nPUBLISHED 14 August 2025  \nDOI 10.3389/fimmu.2025.1653829  \nOPEN ACCESS  \nEDITED BY  \nAfza Ahmad,  \nBabu Banarasi Das University, India  \nREVIEWED BY  \nHaonan Li,  \nUniversity of Electronic Science and Technology of China, China Jaimin R. Shah,  \nUniversity of California, San Diego, United States  \n*CORRESPONDENCE  \nZhiyun Zhang  \n[jianchidaodi_2010@163.com](jianchidaodi_2010@163.com)  \nRECEIVED 25 June 2025  \nACCEPTED 31 July 2025  \nPUBLISHED 14 August 2025  \nCITATION  \nChen C, Li J, Hua X, Deng T and Zhang Z (2025) Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers. Front. Immunol. 16:1653829 .  \ndoi: 10.3389/fimmu.2025.1653829  \nCOPYRIGHT  \n© 2025 Chen, Li, Hua, Deng and Zhang. This isan open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nNano-enabled strategies for targeted immunotherapy in gastrointestinal cancers  \nChaofan Chen 1, Jinlei Li 2, Xiaokun Hua 1, Tingting Deng 1 and Zhiyun Zhang 1*  \n1 Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, China, 2 Department of Orthopedics, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, China  \nGastrointestinal (GI) cancers remain a leading cause of global cancer morbidity and mortality, demanding novel therapeutic strategies that overcome existing limitations. Nanomedicine has recently emerged as a transformative approach, offering the potential to significantly enhance immunotherapy outcomes through precision targeting and modulation of tumour immune microenvironments. This review discusses the principal categories of precision-engineered nanoparticles—including lipid-based carriers, polymeric systems, protein-derived formulations, and metallic-hybrid composites—emphasising their capacity for targeted immune modulation and improved pharmacokinetic profiles. These nanoparticle platforms strategically intervene across multiple stages of the cancer-immunity cycle, facilitating antigen presentation, T-cell activation, and cytotoxic lymphocyte infiltration, and augmenting immune checkpoint blockade efficacy. Clinically approved nanoformulations such as Abraxane, Doxil, Onivyde, and emerging mRNAbased nanovaccines highlight promising translational outcomes in GI malignancies, demonstrating improved therapeutic indices and reduced systemic toxicity. Nonetheless, clinical implementation remains challenged by nano particle complexity, heterogeneous tumour biology, clearance mechanisms, and toxicity concerns. Future success will depend on integrated strategies combining advanced nanoparticle engineering, precise administration routes, rigorous translational validation, and rational therapeutic combinations to realise the full potential of nano medicine-based immunotherapies in gastrointestinal oncology.  \nKEYWORDS  \ngastrointestinal cancers, nanomedicine, tumour microenvironment, precision oncology, immunotherapy  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nIntroduction  \nWorldwide, gastrointestinal (GI) tract cancers accounted for 26.0% of all new cancer diagnoses and 35.0% of cancer-related deaths in 2018 (1) . By 2040, the global incidence of GI cancers is projected to rise to approximately 7.5 million cases annually, resulting in an estimated 5.6 million deaths (2) . In 2020, the lifetime probability of developing and dying from a GI malignancy was 8.20%(95% CI 8.18–8.21) and 6.17%(95% CI 6.16–6.18), respectively. Colorectal","cbCaiebwZGzoUGhG","https://ap.wps.com/l/cbCaiebwZGzoUGhG","pdf",4059313,17,"English","# Introduction\n## Epidemiology and projected burden\n## Immunotherapy promise and limitations\n## Barriers to clinical effectiveness and safety","[{\"question\":\"Why are novel targeted immunotherapy strategies needed for gastrointestinal cancers?\",\"answer\":\"GI cancers remain a major cause of cancer deaths, and existing therapies are limited by suboptimal response rates, safety concerns, and difficulties achieving sustained immune effects.\"},{\"question\":\"What roles do nanomedicine-based platforms play in immunotherapy within this review?\",\"answer\":\"Nanocarriers can precisely modulate tumor immune microenvironments and intervene across the cancer–immunity cycle, enabling improved antigen presentation, T-cell activation, and cytotoxic lymphocyte infiltration.\"},{\"question\":\"What challenges still hinder clinical implementation of nano-enabled immunotherapies?\",\"answer\":\"Clinical translation is constrained by nanoparticle complexity, heterogeneous tumor biology, clearance mechanisms, and toxicity concerns.\"}]","Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers | PDF",1790192866,43]