REVIEW article
Front. Med.
Sec. Gene and Cell Therapy
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1647737
This article is part of the Research TopicInnovations and Challenges in Gene and Cell Therapy: From Bench to BedsideView all articles
Nanotechnology and Natural Killer Cell Immunotherapy: Synergistic Approaches for Precise Immune System Adjustment and Targeted Cancer Treatment in Gastrointestinal Tumors
Provisionally accepted
- 1The First Hospital of China Medical University, Shenyang, China
- 2Harbin Medical University, Harbin, China
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Gastrointestina (GI) tumors are a major contributor to global cancer-related illness and death, marked by their rapid growth, late detection, and resistance to standard treatments. NK cells, key cytotoxic components of the innate immune system, show promise in immunotherapy due to their ability to target tumor cells without requiring antigen presentation. Nonetheless, their effectiveness against gastrointestinal tumors is constrained by issues such as insufficient tumor penetration, brief survival in the body, and suppression by the immunosuppressive tumor microenvironment (TME). Meanwhile, nanotechnology has transformed cancer treatment by offering methods for precise drug delivery, immune system modulation, and improved bioavailability. Combining NK cells with specially designed nanoparticles (NPs) has created a powerful system with amplified cooperative anti-tumor effects, improving the targeting of tumors, activation of NK cells, and their endurance, while also allowing for control over the tumor immune microenvironment in both space and time. This thorough review investigates the complex interaction between the immunobiology of NK cells and the design of nanomaterials, specifically in the context of gastrointestinal tumors. Key areas of focus include nanoparticleassisted engineering of NK cells, cytokine delivery, biomimetic disguise, reprogramming of the TME, and targeting of tumors specifically. We critically assess preclinical and emerging clinical evidence that supports the effectiveness of these combined therapies, analyze related safety and translational challenges, and suggest forward-looking approaches involving gene editing, innovative stimulus-responsive systems, and AI-assisted therapeutic personalization. In conclusion, this review presents the combined NK-NP approach as a promising new frontier in the advancement of personalized, immune-guided treatments for gastrointestinal cancers.
Keywords: Gastrointestinal cancers, NK cells, Immunotherapy, Gastrointestinal tumors, biomimetic nanocarriers, tumor targeting, Stimuli-responsive systems, clinical translation
Received: 16 Jun 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Kang, Li and Sun. This is an 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) or licensor 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.
* Correspondence:
Danyang Li, Harbin Medical University, Harbin, China
Rui Sun, The First Hospital of China Medical University, Shenyang, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.