噬菌体结合纳米材料在多重耐药细菌中的应用进展

doi:10.13560/j.cnki.biotech.bull.1985.2025-0955

生物技术通报

• 综述与专论 • 下一篇

噬菌体结合纳米材料在多重耐药细菌中的应用进展

王明藤¹, 有小娟¹, 孔军珂¹, 李永伟¹^,²(), 张莎莎³, 王庆丰³()

^1.河南中医药大学第二临床医学院河南中医药大学第二附属医院，郑州 450002
^2.河南省中医院检验中心河南省防治耐药菌感染中医药重点实验室郑州市病原微生物与细菌耐药监测重点实验室，郑州 450053
^3.河南省洛阳正骨医院河南省骨科医院，洛阳 471002

收稿日期:2025-09-08 出版日期:2026-04-17 发布日期:2026-04-17
通讯作者: 李永伟lyw@hactcm.edu.cn
王庆丰wangqf600@163.com
作者简介:第一联系人：同等贡献
基金资助:
河南省科技攻关项目(242102310148);吴阶平医学基金会科研专项资助基金(320.6750.2024-03-27);河南省高等学校重点科研项目计划(25A320042)

Advances in Bacteriophage-nanomaterial Synergistic Systems for Antimicrobial Applications against Multidrug-resistant Bacteria

WANG Ming-teng¹, YOU Xiao-juan¹, KONG Jun-ke¹, LI Yong-wei¹^,²(), ZHANG Sha-sha³, WANG Qing-feng³()

^1.The Second Clinical Medical College, Henan University of Chinese Medicine; The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450002
^2.Clinical Laboratory, Henan Province Hospital of Chinese Medicine; Henan Key Laboratory of Traditional Chinese Medicine for Prevention and Control of Drug-Resistant Infections; Zhengzhou Key Laboratory of Pathogenic Microorganisms and Bacterial Drug Resistance, Zhengzhou 450053
^3.Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang 471002

Received:2025-09-08 Published:2026-04-17 Online:2026-04-17

摘要/Abstract

摘要：

全球范围内，多重耐药细菌的持续传播对公共卫生构成严重威胁，传统抗生素疗效持续下降，亟需探索新的抗感染策略。噬菌体可通过特异性识别并裂解宿主细菌发挥精准抗菌作用，但其应用受宿主谱有限、体内稳定性不足及免疫清除等因素制约；纳米材料通过膜破坏、产生活性氧等机制发挥广谱抗菌作用，但其在靶向性和生物相容性方面仍存在不足；二者协同构建的抗菌系统能显著增强对耐药菌感染的抑制效果。围绕噬菌体与纳米材料的协同抗菌作用，现有研究形成了若干具有代表性的组合策略，其差异主要体现在细菌特异性识别、生物膜穿透能力提升及杀菌动力学改善等方面。本文在系统梳理相关研究进展的基础上，对不同协同模式的作用特点、应用场景及研究局限进行了归纳比较。目前该策略临床转化仍面临噬菌体免疫原性、纳米材料生物相容性、规模化制备一致性及质量控制等因素的影响。未来研究应聚焦于噬菌体定向进化与修饰、可降解纳米载体开发以及标准化生产流程建立，以促进其向临床应用转化，为控制耐药菌感染提供新路径。

关键词: 噬菌体疗法, 多重耐药细菌, 纳米材料, 联合抗菌疗法

Abstract:

The continuous global spread of multidrug-resistant bacteria poses a serious threat to public health, while the effectiveness of conventional antibiotics continues to decline, underscoring the urgent need for alternative antimicrobial strategies. Bacteriophages exert precise antibacterial activity by specifically recognizing and lysing host bacteria; however, their application is constrained by a narrow host range, limited in vivo stability, and immune clearance. Nanomaterials present broad-spectrum antibacterial effects through mechanisms such as membrane disruption and reactive oxygen species generation, but challenges remain regarding targeting efficiency and biocompatibility. Synergistic antibacterial systems constructed by integrating bacteriophages with nanomaterials can significantly enhance the suppression of drug-resistant bacterial infections. Focusing on the synergistic antibacterial effects of bacteriophages and nanomaterials, current studies have developed several representative combination strategies. Based on a systematic review of relevant research progress, this paper summarizes and compares the characteristics, application scenarios, and research limitations of different synergistic modes. Currently, the clinical translation of this strategy is still challenged by factors such as phage immunogenicity, biocompatibility of nanomaterials, consistency of large-scale preparation, and quality control. Future research should focus on the directed evolution and modification of bacteriophages, the development of biodegradable nanocarriers, and the establishment of standardized production workflows, thereby facilitating clinical translation and providing new avenues for the control of multidrug-resistant bacterial infections.

Key words: bacteriophage therapy, multidrug-resistant bacteria, nanomaterials, combined antimicrobial therapy

王明藤, 有小娟, 孔军珂, 李永伟, 张莎莎, 王庆丰. 噬菌体结合纳米材料在多重耐药细菌中的应用进展[J]. 生物技术通报, doi: 10.13560/j.cnki.biotech.bull.1985.2025-0955.

WANG Ming-teng, YOU Xiao-juan, KONG Jun-ke, LI Yong-wei, ZHANG Sha-sha, WANG Qing-feng. Advances in Bacteriophage-nanomaterial Synergistic Systems for Antimicrobial Applications against Multidrug-resistant Bacteria[J]. Biotechnology Bulletin, doi: 10.13560/j.cnki.biotech.bull.1985.2025-0955.

图/表 4

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协同策略 Collaborative strategy	模型/病原体 Model/Pathogen	关键效能指标 Key performance indicators	核心优势 Core advantages	主要局限 Main limitations
物理结合与空间共定位	小鼠角膜炎	眼部滞留时间最长12 h；角膜透明度和细胞修复显著改善^［29］	增强稳定性+靶向黏附	规模化制备难度高
噬菌体导向靶向递送	金黄色葡萄球菌生物膜	生物膜强度减少95%；联合处理后存活率降至14%^［32］	精准定位感染灶	RBP宿主特异性限制
光热/酶响应级联激活	铜绿假单胞菌感染伤口	10 min内目标细菌完全失活；非目标细菌保留^［34］	时空可控治疗	近红外设备依赖性强
基因编辑联合清除	MRSA肺炎模型	细菌负荷降至<100 CFU/mL；炎症指标接近正常^［37］	逆转耐药性+协同杀菌	CRISPR脱靶风险
仿生纳米涂层免疫屏蔽	沙门氏菌肠炎模型	细胞内噬菌体裂解效率更高，清除生物膜并改善炎症^［38］	突破胃肠屏障+免疫逃逸	涂层材料降解可控性待优化
微生态重塑	DSS结肠炎小鼠	细胞存活率由40%升至85%；炎症因子下调，益生因子上调^［43］	避免菌群失调+生态修复	菌群互作网络调控复杂

协同策略 Collaborative strategy	模型/病原体 Model/Pathogen	关键效能指标 Key performance indicators	核心优势 Core advantages	主要局限 Main limitations
物理结合与空间共定位	小鼠角膜炎	眼部滞留时间最长12 h；角膜透明度和细胞修复显著改善^［29］	增强稳定性+靶向黏附	规模化制备难度高
噬菌体导向靶向递送	金黄色葡萄球菌生物膜	生物膜强度减少95%；联合处理后存活率降至14%^［32］	精准定位感染灶	RBP宿主特异性限制
光热/酶响应级联激活	铜绿假单胞菌感染伤口	10 min内目标细菌完全失活；非目标细菌保留^［34］	时空可控治疗	近红外设备依赖性强
基因编辑联合清除	MRSA肺炎模型	细菌负荷降至<100 CFU/mL；炎症指标接近正常^［37］	逆转耐药性+协同杀菌	CRISPR脱靶风险
仿生纳米涂层免疫屏蔽	沙门氏菌肠炎模型	细胞内噬菌体裂解效率更高，清除生物膜并改善炎症^［38］	突破胃肠屏障+免疫逃逸	涂层材料降解可控性待优化
微生态重塑	DSS结肠炎小鼠	细胞存活率由40%升至85%；炎症因子下调，益生因子上调^［43］	避免菌群失调+生态修复	菌群互作网络调控复杂

协同策略 Combination strategy	生物安全性风险 Biosafety risk	生产可扩展性 Manufacturing scalability	成本可控性 Cost controllability	监管复杂度 Regulatory complexity	近期临床可行性 Short-term clinical feasibility
物理结合与空间共定位	低-中	中-高	中	低-中	较高
噬菌体导向靶向递送	中	中	中	中	中-较高
光热/酶响应级联激活	中	中	中-低	中-高	中
基因编辑联合清除	高	低	低	高	较低
仿生纳米涂层免疫屏蔽	低-中	中	中	中	较高
微生态重塑	中	中-低	中	中-高	中

协同策略 Combination strategy	生物安全性风险 Biosafety risk	生产可扩展性 Manufacturing scalability	成本可控性 Cost controllability	监管复杂度 Regulatory complexity	近期临床可行性 Short-term clinical feasibility
物理结合与空间共定位	低-中	中-高	中	低-中	较高
噬菌体导向靶向递送	中	中	中	中	中-较高
光热/酶响应级联激活	中	中	中-低	中-高	中
基因编辑联合清除	高	低	低	高	较低
仿生纳米涂层免疫屏蔽	低-中	中	中	中	较高
微生态重塑	中	中-低	中	中-高	中

噬菌体结合纳米材料在多重耐药细菌中的应用进展

Advances in Bacteriophage-nanomaterial Synergistic Systems for Antimicrobial Applications against Multidrug-resistant Bacteria

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