佩戴带有可装载药物的粘性纳米头盔的噬菌体以治疗眼部感染。
Wearing bacteriophages individually with an adhesive drug-loadable nanohelmet for treating ocular infections.
作者信息
Meng Lu, Yang Fengmin, Cao Zhenping, Wang Chuhan, Chen Ju, Zhu Yufeng, Wang Kexin, Liu Jinyao, Yan Deyue, Pang Yan
机构信息
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Institute of Molecular Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
出版信息
Sci Adv. 2025 Jul 11;11(28):eadx4183. doi: 10.1126/sciadv.adx4183.
Ocular infections pose notable blindness risks. Despite its advantages in inhibiting multidrug-resistant bacteria and eliminating biofilms, phage therapy suffers low phage vitality, limited ocular retention, and lack of anti-inflammatory abilities toward ocular infections. Here, wearing phages individually with an adhesive drug-loadable nanohelmet is reported to advance phage therapy. The nanohelmet is formed by depositing arginine-glycine-aspartic acid-modified chitosan on negatively charged phage head through electrostatic interactions, followed by codepositing anti-inflammatory agents via physical adsorption. Nanohelmet formation shows a negligible influence on phage vitality and is applicable to helmet diverse phages. Because of the cationic nature and the presence of arginine-glycine-aspartic acid sequence, such nanohelmet exhibits a double-lock adhesion fashion to ocular surface, prolonging phage retention after instillation. Together with sustained drug release, helmeted phages potently inhibit bacteria, eliminate biofilms, and effectively suppress localized inflammation. In mice with multidrug-resistant pathogen-induced keratitis, helmeted phages achieve superior therapeutic efficacies, even compared to clinical therapeutics.
眼部感染带来显著的致盲风险。尽管噬菌体疗法在抑制多重耐药菌和消除生物膜方面具有优势,但它存在噬菌体活力低、眼部滞留时间有限以及对眼部感染缺乏抗炎能力等问题。在此,报告了通过将噬菌体单独与可负载药物的粘性纳米头盔结合来推进噬菌体疗法。纳米头盔是通过静电相互作用将精氨酸 - 甘氨酸 - 天冬氨酸修饰的壳聚糖沉积在带负电荷的噬菌体头部形成的,随后通过物理吸附共沉积抗炎剂。纳米头盔的形成对噬菌体活力的影响可忽略不计,并且适用于多种噬菌体。由于其阳离子性质以及精氨酸 - 甘氨酸 - 天冬氨酸序列的存在,这种纳米头盔对眼表呈现双锁粘附方式,延长了滴注后噬菌体的滞留时间。与药物的持续释放一起,带纳米头盔的噬菌体能够有效抑制细菌、消除生物膜并有效抑制局部炎症。在多重耐药病原体诱导的角膜炎小鼠中,带纳米头盔的噬菌体即使与临床治疗药物相比也能实现卓越的治疗效果。