Softness enhanced macrophage-mediated therapy of inhaled apoptotic-cell-inspired nanosystems for acute lung injury

Journal of Nanobiotechnology

Research

Mingyang Xie¹  Xiangchao Liang¹  Dazheng Sun¹  Mei Tu¹  Rong Zeng¹  Guanglin Zhang²  Yina Wang³  Zhijian Su³ 

[1] Department of Materials Science and Engineering, College of Chemistry and Materials, Jinan University, 510632, Guangzhou, P. R. China;Department of Materials Science and Engineering, College of Chemistry and Materials, Jinan University, 510632, Guangzhou, P. R. China;Henry Fok Colloge of Biology and Agriculture, Shaoguan University, 512005, Shaoguan, P. R. China;Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, 510632, Guangzhou, P. R. China;National Engineering Research Center of Genetic Medicine, Jinan University, 510632, Guangzhou, P. R. China;

关键词: Softness;    Apoptotic-cell-inspired;    Macrophage;    Anti-inflammatory;    Acute lung injury;   

DOI  :  10.1186/s12951-023-01930-2

 received in 2023-02-09, accepted in 2023-05-14,  发布年份 2023

来源: Springer

【 摘 要 】

Engineered nanosystems offer a promising strategy for macrophage-targeted therapies for various diseases, and their physicochemical parameters including surface-active ligands, size and shape are widely investigated for improving their therapeutic efficacy. However, little is known about the synergistic effect of elasticity and surface-active ligands. Here, two kinds of anti-inflammatory N-acetylcysteine (NAC)-loaded macrophage-targeting apoptotic-cell-inspired phosphatidylserine (PS)-containing nano-liposomes (PSLipos) were constructed, which had similar size and morphology but different Young’s modulus (E) (H, ~ 100 kPa > Emacrophage vs. L, ~ 2 kPa < Emacrophage). Interestingly, these PSLipos-NAC showed similar drug loading and encapsulation efficiency, and in vitro slow-release behavior of NAC, but modulus-dependent interactions with macrophages. Softer PSLipos-L-NAC could resist macrophage capture, but remarkably prolong their targeting effect period on macrophages via durable binding to macrophage surface, and subsequently more effectively suppress inflammatory response in macrophages and then hasten inflammatory lung epithelial cell wound healing. Especially, pulmonary administration of PSLipos-L-NAC could significantly reduce the inflammatory response of M1-like macrophages in lung tissue and promote lung injury repair in a bleomycin-induced acute lung injury (ALI) mouse model, providing a potential therapeutic approach for ALI. The results strongly suggest that softness may enhance ligand-directed macrophage-mediated therapeutic efficacy of nanosystems, which will shed new light on the design of engineered nanotherapeutics.Graphical abstract

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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Fig. 1