Current pharmacotherapy remains futile in acute alveolar inflammation induced by Gram-negative bacteria (GNB), eliciting consequent respiratory failure. The release of lipid polysaccharides after antibiotic treatment and subsequent progress of proinflammatory cascade highlights the necessity to apply effective inflammation management simultaneously. This work describes modular self-assembling peptides for rapid anti-inflammatory programming (SPRAY) to form nanoparticles targeting macrophage specifically, having anti-inflammation and bactericidal functions synchronously. SPRAY nanoparticles accelerate the self-delivery process in macrophages via lysosomal membrane permeabilization, maintaining anti-inflammatory programming in macrophages with efficacy close to T helper 2 cytokines. By pulmonary deposition, SPRAY nanoparticles effectively suppress inflammatory infiltration and promote alveoli regeneration in murine aseptic acute lung injury. Moreover, SPRAY nanoparticles efficiently eradicate multidrug-resistant GNB in alveoli by disrupting bacterial membrane. The universal molecular design of SPRAY nanoparticles provides a robust and clinically unseen local strategy in reverse acute inflammation featured by a high accumulation of proinflammatory cellularity and drug-resistant bacteria.

中文翻译：

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模块化肽组件的可吸入 SPRAY 纳米颗粒可逆转致命革兰氏阴性菌感染中的肺泡炎症


目前的药物治疗对革兰氏阴性菌 （GNB） 诱导的急性肺泡炎症仍然无效，从而导致呼吸衰竭。抗生素治疗后脂质多糖的释放和随后的促炎级联反应的进展突出了同时应用有效炎症管理的必要性。这项工作描述了用于快速抗炎编程 （SPRAY） 的模块化自组装肽，以形成专门针对巨噬细胞的纳米颗粒，同时具有抗炎和杀菌功能。SPRAY 纳米颗粒通过溶酶体膜透化加速巨噬细胞中的自我递送过程，维持巨噬细胞中的抗炎程序，其功效接近辅助性 T 细胞 2 细胞因子。通过肺沉积，SPRAY 纳米颗粒有效抑制小鼠无菌性急性肺损伤的炎症浸润并促进肺泡再生。此外，SPRAY 纳米颗粒通过破坏细菌膜有效地根除肺泡中的多重耐药 GNB。SPRAY 纳米颗粒的通用分子设计为逆转急性炎症提供了一种强大且临床上看不见的局部策略，其特征是促炎细胞和耐药细菌的高度积累。