Kang Xiwen, Li Danyang, Sun Rui
Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, China.
Department of Pharmacology, Harbin Medical University, Harbin, China.
Front Med (Lausanne). 2025 Aug 21;12:1647737. doi: 10.3389/fmed.2025.1647737. eCollection 2025.
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, 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 nanoparticle-assisted 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.
胃肠道（GI）肿瘤是全球癌症相关疾病和死亡的主要原因，其特点是生长迅速、发现较晚且对标准治疗有抗性。自然杀伤（NK）细胞是先天免疫系统的关键细胞毒性成分，由于其能够在无需抗原呈递的情况下靶向肿瘤细胞，因此在免疫治疗中显示出前景。尽管如此，它们对胃肠道肿瘤的有效性受到诸如肿瘤穿透不足、体内存活以及免疫抑制性肿瘤微环境（TME）抑制等问题的限制。同时，纳米技术通过提供精确药物递送、免疫系统调节和提高生物利用度的方法，改变了癌症治疗。将NK细胞与特殊设计的纳米颗粒（NPs）相结合，创造了一个强大的系统，具有增强的协同抗肿瘤作用，改善了肿瘤靶向性、NK细胞的激活及其耐受性，同时还能在空间和时间上控制肿瘤免疫微环境。这篇全面的综述研究了NK细胞免疫生物学与纳米材料设计之间的复杂相互作用，特别是在胃肠道肿瘤的背景下。重点关注的关键领域包括NK细胞的纳米颗粒辅助工程、细胞因子递送、仿生伪装、TME的重编程以及肿瘤的特异性靶向。我们批判性地评估了支持这些联合疗法有效性的临床前和新兴临床证据，分析了相关的安全性和转化挑战，并提出了涉及基因编辑、创新的刺激响应系统和人工智能辅助治疗个性化的前瞻性方法。总之，本综述将NK-NP联合方法呈现为胃肠道癌症个性化免疫导向治疗进展中一个有前景的新领域。
