头孢他啶辅助合成超小壳聚糖纳米颗粒,用于穿透生物膜和根除绿脓杆菌。
Ceftazidime-assisted synthesis of ultrasmall chitosan nanoparticles for biofilm penetration and eradication of Pseudomonas aeruginosa.
发表日期:2023 Aug 18
作者:
Xiaoran Zheng, Min Gao, Liangquan Wu, Xin Lu, Qiuqi Lin, Hai Zhong, Yingfei Lu, Yunlei Zhang, Xiuwei Zhang
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
绿脓杆菌感染对免疫受损个体,特别是囊性纤维化患者,构成了严重威胁,因为该菌可形成细菌生物膜。本研究中,我们设计了能够有效穿透生物膜并根除绿脓杆菌的自组装壳聚糖头孢他啶纳米颗粒(CSCE)。通过离子交联合成了CSCE纳米颗粒,将带负电荷的头孢他啶与带正电荷的壳聚糖结合,形成了直径约为40 nm的均匀纳米颗粒,具有高度分散性和良好生物相容性。显著的是,这些纳米颗粒对绿脓杆菌的生长具有明显的抑制作用,降低了吲哚蓝的产生,减少了生物膜的形成,最大抑制率达到了22.44%。此外,体内实验表明,给予CSCE纳米颗粒治疗的腹腔绿脓杆菌感染小鼠生存率提高,伴随着炎症因子白细胞介素-6 (125.79±18.63 pg/mL)、白细胞介素-17 (125.67±5.94 pg/mL)和肿瘤坏死因子-α (135.4±11.77 pg/mL)水平的降低。至关重要的是,在腹腔注射绿脓杆菌感染后,接受CSCE纳米颗粒治疗的小鼠血液中无菌。总的来说,我们的研究结果强调了这些合成纳米颗粒作为抗绿脓杆菌感染剂的潜力。© 2023. Springer Nature Limited.
Pseudomonas aeruginosa (P. aeruginosa) infections present a grave threat to immunocompromised individuals, particularly those with cystic fibrosis due to the development of bacterial biofilms. In this study, we engineered self-assembling chitosan-ceftazidime nanoparticles (CSCE) capable of effectively penetrating biofilms and eradicating P. aeruginosa. The CSCE nanoparticles were synthesized through ionic cross-linking, combining negatively charged ceftazidime with positively charged chitosan, resulting in uniform nanoparticles measuring approximately 40 nm in diameter, exhibiting high dispersity and excellent biocompatibility. Remarkably, these nanoparticles exhibited significant inhibition of P. aeruginosa growth, reduced pyocyanin production, and diminished biofilm formation, achieving a maximum inhibition rate of 22.44%. Furthermore, in vivo investigations demonstrated enhanced survival in mice with abdominal P. aeruginosa infection following treatment with CSCE nanoparticles, accompanied by reduced levels of inflammatory cytokines Interleukin-6 (125.79 ± 18.63 pg/mL), Interleukin-17 (125.67 ± 5.94 pg/mL), and Tumor Necrosis Factor-α (135.4 ± 11.77 pg/mL). Critically, mice treated with CSCE nanoparticles showed no presence of bacteria in the bloodstream following intraperitoneal P. aeruginosa infection. Collectively, our findings highlight the potential of these synthesized nanoparticles as effective agents against P. aeruginosa infections.© 2023. Springer Nature Limited.