Nanoplatforms for Sepsis Management: Rapid Detection/Warning, Pathogen Elimination and Restoring Immune Homeostasis

Abstract

Sepsis, a highly life-threatening organ dysfunction caused by uncontrollable immune responses to infection, is a leading contributor to mortality in intensive care units. Sepsis-related deaths have been reported to account for 19.7% of all global deaths. However, no effective and specific therapeutic for clinical sepsis management is available due to the complex pathogenesis. Concurrently eliminating infections and restoring immune homeostasis are regarded as the core strategies to manage sepsis. Sophisticated nanoplatforms guided by supramolecular and medicinal chemistry, targeting infection and/or imbalanced immune responses, have emerged as potent tools to combat sepsis by supporting more accurate diagnosis and precision treatment. Nanoplatforms can overcome the barriers faced by clinical strategies, including delayed diagnosis, drug resistance and incapacity to manage immune disorders. Here, we present a comprehensive review highlighting the pathogenetic characteristics of sepsis and future therapeutic concepts, summarizing the progress of these well-designed nanoplatforms in sepsis management and discussing the ongoing challenges and perspectives regarding future potential therapies. Based on these state-of-the-art studies, this review will advance multidisciplinary collaboration and drive clinical translation to remedy sepsis."Image missing"

A Multifunctional Nanoparticle Mitigating Cytokine Storm by Scavenging Multiple Inflammatory Mediators of Sepsis

“…The synergistic scavenging resulted in a better anti-inflammatory effect, which also reflected the advantage of materials with the ability to scavenge multiple inflammatory mediators. Overexpression of NO by inducible nitric oxide synthase (iNOS) contributed to excessive inflammation in sepsis . We also illustrated the anti-inflammatory ability of TMPP by changes in NO content at the cellular level, where the content of NO in the cell culture while supernatant increased significantly after LPS stimulation, but NO production was significantly inhibited by the addition of TMPP (Figure S14B).…”

Biomimetic Immunosuppressive Exosomes that Inhibit Cytokine Storms Contribute to the Alleviation of Sepsis

“…Most studies have focused on the exosome-mediated transport of micro-RNAs and proteins. [15,16] Further, current research has focused on the functions of "natural" exosomes, such as those secreted by adipose tissue-derived stem cells, which can reduce vascular leakage and improve organ function by regulating the Nrf2/HO-1 axis to polarize macrophages into anti-inflammatory phenotypes, thus suppressing sepsis-associated inflammation and organ damage. [17] Exogenous endothelial progenitor cell derived exosomes offer protection against sepsis by reducing vascular leakage and improving organ function.…”

Multiple datasets to explore the molecular mechanism of sepsis

“…In previous genomic and transcriptomic studies, many studies have focused on the differences between septic patients and healthy individuals [ 3 ], but there are insufficient studies on the mechanism of action of septic shock. Studies have shown that early warning and identification of risk factors for patients with sepsis can lead to faster and more accurate standardized treatment, which is helpful for the diagnosis, treatment and prognosis of sepsis [ 4 ].…”