Macrophages-regulating nanomedicines for sepsis therapy

Sepsis is the leading cause of death in intensive care unit (ICU), which is caused by deregulated im-mune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and support-ive care, while there still lacks of specific molecular therapy. As a type of immune dysfunction disease, macrophages have been recognized as the key immune cells precipitating in the whole process of sepsis, which is activated into M1-like to trigger various inflammatory responses at early stage whereas polar-ized into M2-like to cause immunosuppression in later stage. Therefore, great attention has been paid on the design of nanomedicines to regulate the functions of macrophages for etiological treatment of sep-sis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavail-ability, targetability, reduced side-effects. This critical review aims to summarize the recent progress of macrophages-regulating nanoparticles for sepsis therapy. First, the essential roles of macrophages in the development and progression of sepsis have been introduced, including the positive roles of macrophages to combat infections and dysfunction of macrophages to cause body damages. We then focus our main attention to discuss the nanomedicines with different therapeutic mechanisms corresponding to each stage of sepsis, such as infection blockage, inflammation inhibition, immune functions recovery, as well as multifunctional nanomedicines. Finally, a few limitations of current nanomedicines are highlighted, and future perspective are speculated for potential clinical translation, which might pave the way for the development of macrophages-centered nanomedicines for more effective sepsis therapy.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Sepsis, the leading cause of death in ICU, is caused by deregulated immune responses to pathogen infection. Macrophages, as key immune cells, play essential roles in sepsis development and progression. Nanomedicines are designed to regulate macrophage functions for more effective sepsis therapy, with the advantages of enhanced drug bioavailability, targetability, and reduced side-effects. This review summarizes the recent progress of macrophage-regulating nanoparticles for sepsis treatment.