具有葡萄糖氧化酶增强光声成像和光热效应的酸性可激活纳米颗粒，以及用于生物膜感染协同治疗的巨噬细胞相关免疫调节,Small

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具有葡萄糖氧化酶增强光声成像和光热效应的酸性可激活纳米颗粒，以及用于生物膜感染协同治疗的巨噬细胞相关免疫调节
Small ( IF 13.0 ) Pub Date : 2022-10-10 , DOI: 10.1002/smll.202204377
Yong Dai ₁ , Jiawei Mei ₁ , Zhe Li ₂ , Lingtong Kong ₁ , Wanbo Zhu ₁ , Qianming Li ₁ , Kerong Wu ₁ , Yan Huang ₁ , Xifu Shang ₁ , Chen Zhu ₁

Affiliation

pH响应性诊断学在疾病的精确诊断和治疗方面具有巨大潜力。在此，开发了基于葡萄糖氧化酶（GO）和聚苯胺的酸度可激活纳米颗粒 GB@P 用于治疗生物膜感染。在 GO 的催化下，GB@P 触发葡萄糖转化为葡萄糖酸和过氧化氢 (H ₂ O ₂ )，从而实现同时激活的酸性微环境增强光热 (PT) 效应/放大光声成像 (PAI)。_{GB@P 和 H 2} O ₂增强的 PT 功效的协同作用加速了生物膜的根除，因为 H ₂ O _2的渗透进入生物膜提高了细菌对热的敏感性，增强的 PT 效应破坏了细胞外 DNA 和基因组 DNA 的表达，导致生物膜破坏和细菌死亡。重要的是，GB@P 促进促炎 M1 巨噬细胞的极化，启动巨噬细胞相关免疫，增强巨噬细胞的吞噬作用和促炎细胞因子的分泌，通过先天免疫调节作用产生持续的杀菌作用和生物膜根除。因此，GB@P 的纳米平台通过增强的 PT 效应与免疫调节相结合，表现出对生物膜根除和细菌残留物清除的协同作用。

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Acidity-Activatable Nanoparticles with Glucose Oxidase-Enhanced Photoacoustic Imaging and Photothermal Effect, and Macrophage-Related Immunomodulation for Synergistic Treatment of Biofilm Infection

The pH-responsive theragnostics exhibit great potential for precision diagnosis and treatment of diseases. Herein, acidity-activatable nanoparticles of GB@P based on glucose oxidase (GO) and polyaniline are developed for treatment of biofilm infection. Catalyzed by GO, GB@P triggers the conversion of glucose into gluconic acid and hydrogen peroxide (H₂O₂), enabling an acidic microenvironment-activated simultaneously enhanced photothermal (PT) effect/amplified photoacoustic imaging (PAI). The synergistic effects of the enhanced PT efficacy of GB@P and H₂O₂ accelerate biofilm eradication because the penetration of H₂O₂ into biofilm improves the bacterial sensitivity to heat, and the enhanced PT effect destroys the expressions of extracellular DNA and genomic DNA, resulting in biofilm destruction and bacterial death. Importantly, GB@P facilitates the polarization of proinflammatory M1 macrophages that initiates macrophage-related immunity, which enhances the phagocytosis of macrophages and secretion of proinflammatory cytokines, leading to a sustained bactericidal effect and biofilm eradication by the innate immunomodulatory effect. Accordingly, the nanoplatform of GB@P exhibits the synergistic effects on the biofilm eradication and bacterial residuals clearance through a combination of the enhanced PT effect with immunomodulation. This study provides a promising nanoplatform with enhanced PT efficacy and amplified PAI for diagnosis and treatment of biofilm infection.

更新日期：2022-10-10

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