Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers

Gastrointestinal (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 outc...

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Main Authors: Chaofan Chen, Jinlei Li, Xiaokun Hua, Tingting Deng, Zhiyun Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1653829/full
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author Chaofan Chen
Jinlei Li
Xiaokun Hua
Tingting Deng
Zhiyun Zhang
author_facet Chaofan Chen
Jinlei Li
Xiaokun Hua
Tingting Deng
Zhiyun Zhang
author_sort Chaofan Chen
collection DOAJ
description Gastrointestinal (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 mRNA-based nanovaccines highlight promising translational outcomes in GI malignancies, demonstrating improved therapeutic indices and reduced systemic toxicity. Nonetheless, clinical implementation remains challenged by nanoparticle 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 nanomedicine-based immunotherapies in gastrointestinal oncology.
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spelling doaj-art-d63e65a080e24dba87721e1b0b5bc1252025-08-20T03:36:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16538291653829Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancersChaofan Chen0Jinlei Li1Xiaokun Hua2Tingting Deng3Zhiyun Zhang4Department of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaDepartment of Orthopedics, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaDepartment of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaDepartment of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaDepartment of Anorectal, Kunming Municipal Hospital of Traditional Chinese Medicine, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, ChinaGastrointestinal (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 mRNA-based nanovaccines highlight promising translational outcomes in GI malignancies, demonstrating improved therapeutic indices and reduced systemic toxicity. Nonetheless, clinical implementation remains challenged by nanoparticle 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 nanomedicine-based immunotherapies in gastrointestinal oncology.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1653829/fullgastrointestinal cancersnanomedicinetumour microenvironmentprecision oncologyimmunotherapy
spellingShingle Chaofan Chen
Jinlei Li
Xiaokun Hua
Tingting Deng
Zhiyun Zhang
Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers
Frontiers in Immunology
gastrointestinal cancers
nanomedicine
tumour microenvironment
precision oncology
immunotherapy
title Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers
title_full Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers
title_fullStr Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers
title_full_unstemmed Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers
title_short Nano-enabled strategies for targeted immunotherapy in gastrointestinal cancers
title_sort nano enabled strategies for targeted immunotherapy in gastrointestinal cancers
topic gastrointestinal cancers
nanomedicine
tumour microenvironment
precision oncology
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1653829/full
work_keys_str_mv AT chaofanchen nanoenabledstrategiesfortargetedimmunotherapyingastrointestinalcancers
AT jinleili nanoenabledstrategiesfortargetedimmunotherapyingastrointestinalcancers
AT xiaokunhua nanoenabledstrategiesfortargetedimmunotherapyingastrointestinalcancers
AT tingtingdeng nanoenabledstrategiesfortargetedimmunotherapyingastrointestinalcancers
AT zhiyunzhang nanoenabledstrategiesfortargetedimmunotherapyingastrointestinalcancers