Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive care, whi...Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive 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 polarized 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 sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, 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.展开更多
The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging(MRI),with the advantage of significantly improved specificity and good biocompatibility.However,t...The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging(MRI),with the advantage of significantly improved specificity and good biocompatibility.However,the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor progression.Here,we report on a dual-ratiometric magnetic resonance tunable(DMRT)nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles,complexed to a pH responsive biocompatible polymer.This dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization,providing exceptional quantitative pathophysiological information in vitro and in vivo.When used in combination with dual-contrast enhancement triple subtraction imaging technique(DETSI),this smart nanoprobe guarantees the diagnosis of early-stage diseases.We envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging,as well as microenvironment visualization and disease progression monitoring.展开更多
基金supported by National Natural Science Foundation of China(Nos.U1903125,82073799)Natural Science Foundation of Hunan Province in China(Nos.2021JJ20084,2021JJ70016)the Science and Technology Innovation Program of Hunan Province(No.2021RC3020)。
文摘Sepsis is the leading cause of death in intensive care unit(ICU), which is caused by deregulated immune responses to pathogens infection. Clinically, sepsis treatment is limited to antibiotics and supportive 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 polarized 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 sepsis, by virtue of the unique advantages of nano-drug delivery systems, such as enhanced drug bioavailability, 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.
基金This work was supported by the National Natural Science Foundation of China(Nos.81971664 and 82272057)the Shanghai Pujiang Program(No.2019PJD044).
文摘The development of microenvironment-responsive nanoprobes has shown great promise for use in magnetic resonance imaging(MRI),with the advantage of significantly improved specificity and good biocompatibility.However,the clinical application of responsive probes is hampered by a lack of biological sensitivity for early molecular diagnostics and visualizing microenvionment of metabolism reprogramming in tumor progression.Here,we report on a dual-ratiometric magnetic resonance tunable(DMRT)nanoprobe designed by crosslinking different ratios of transferrin chelating gadolinium and superparamagnetic nanoparticles,complexed to a pH responsive biocompatible polymer.This dually activatable nanoprobe enables pH-dependent tumor microenvironment visualization,providing exceptional quantitative pathophysiological information in vitro and in vivo.When used in combination with dual-contrast enhancement triple subtraction imaging technique(DETSI),this smart nanoprobe guarantees the diagnosis of early-stage diseases.We envisage that this novel integrated nanoplatform will provide a new paradigm for the clinical translation of robust DMRT nanoprobes for early disease detection and staging,as well as microenvironment visualization and disease progression monitoring.
