Song Xianhui, Li Jie, Huang Siyuan, Zhang Yufei, Hong Shihao, Zhang Xinge
Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
Small. 2025 May 30:e2501131. doi: 10.1002/smll.202501131.
The emergence of drug resistance in bacteria, along with the protective nature and intricate environment of biofilms, impedes the effective treatment of severe bacterial infections, posing significant health risks. Herein, a coordination polymer nanoparticle (LZC) is fabricated via a facile in situ strategy for sonodynamic therapy (SDT) combating drug-resistant bacteria-induced infections. By conjugating the Food and Drug Administration (FDA)-approved safe sonosensitizer porphyrin chlorin e6 (Ce6) with a positively charged antimicrobial peptide LL37 through coordination interaction, the resultant LZC exhibits uniform size and a positively charged surface, which is beneficial for the efficient capture of bacteria and improved nanoparticle penetration into biofilms. Under ultrasound (US) stimuli, the nanoparticle generates a higher reactive oxygen species (ROS) compared with the free sonosensitizers, as well as the production of heat, leading to bacterial cell death and biofilm disruption. In vitro evaluations reveal the robust antibacterial activity of LZC, achieving up to 99% eradication of multi-drug resistant Pseudomonas aeruginosa (MDRPA) and significant biofilm eradication under deep-penetrating US irradiation. Moreover, the establishment of coordination polymer nanoparticles represents an innovative strategy to enhance SDT in an MDRPA-induced-pneumonia mice model and provides a great promise for advancing therapeutic interventions in deep tissue bacterial infections.
细菌耐药性的出现，以及生物膜的保护性和复杂环境，阻碍了严重细菌感染的有效治疗，带来了重大的健康风险。在此，通过一种简便的原位策略制备了一种配位聚合物纳米颗粒（LZC），用于声动力疗法（SDT）对抗耐药细菌引起的感染。通过配位相互作用将美国食品药品监督管理局（FDA）批准的安全声敏剂卟啉氯e6（Ce6）与带正电荷的抗菌肽LL37偶联，所得的LZC呈现出均匀的尺寸和带正电荷的表面，这有利于高效捕获细菌并提高纳米颗粒对生物膜的穿透能力。在超声（US）刺激下，与游离声敏剂相比，该纳米颗粒产生更高的活性氧（ROS），同时还产生热量，导致细菌细胞死亡和生物膜破坏。体外评估揭示了LZC强大的抗菌活性，在深度穿透的US照射下能够实现高达99%的多重耐药铜绿假单胞菌（MDRPA）根除率以及显著的生物膜根除效果。此外，配位聚合物纳米颗粒的建立代表了一种创新策略，可在MDRPA诱导的肺炎小鼠模型中增强SDT，并为推进深部组织细菌感染的治疗干预提供了巨大希望。
