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

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

Abstract

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

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.

Figures/Tables 4

References 71

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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