Rheumatoid arthritis microenvironment insights into treatment effect of nanomaterials

Sepsis is a systemic inflammatory response syndrome with high morbidity and mortality mediated by infection-caused oxidative stress. Early antioxidant intervention by removing excessively produced reactive oxygen and nitrogen species (RONS) is beneficial to the prevention and treatment of sepsis. However, traditional antioxidants have failed to improve patient outcomes due to insufficient activity and sustainability. Herein, by mimicking the electronic and structural characteristics of natural Cu-only superoxide dismutase (SOD5), a single-atom nanozyme (SAzyme) featuring coordinately unsaturated and atomically dispersed Cu-N4 site was synthesized for effective sepsis treatment. The de novo-designed Cu-SAzyme exhibits a superior SOD-like activity to efficiently eliminate O2•-, which is the source of multiple RONS, thus blocking the free radical chain reaction and subsequent inflammatory response in the early stage of sepsis. Moreover, the Cu-SAzyme effectively harnessed systemic inflammation and multi-organ injuries in sepsis animal models. These findings indicate that the developed Cu-SAzyme possesses great potential as therapeutic nanomedicines for the treatment of sepsis. 

Bioinspired copper single‐atom nanozyme as a superoxide dismutase‐like antioxidant for sepsis treatment

SARS-CoV-2 has caused up to 127 million cases of COVID-19. Approximately 5% of COVID-19 patients develop severe illness, and approximately 40% of those with severe illness eventually die, corresponding to more than 2.78 million people. The pathological characteristics of COVID-19 resemble typical sepsis, and severe COVID-19 has been identified as viral sepsis. Progress in sepsis research is important for improving the clinical care of these patients. Recent advances in understanding the pathogenesis of sepsis have led to the view that an uncontrolled inflammatory response and oxidative stress are core factors. However, in the traditional treatment of sepsis, it is difficult to achieve a balance between the inflammation, pathogens (viruses, bacteria, and fungi), and patient tolerance, resulting in high mortality of patients with sepsis. In recent years, nanomaterials mediating reactive oxygen and nitrogen species (RONS) and the inflammatory response have shown previously unattainable therapeutic effects on sepsis. Despite these advantages, RONS and inflammatory response-based nanomaterials have yet to be extensively adopted as sepsis therapy. To the best of our knowledge, no review has yet discussed the pathogenesis of sepsis and the application of nanomaterials. To help bridge this gap, we discuss the pathogenesis of sepsis related to inflammation and the overproduction RONS, which activate pathogen-associated molecular pattern (PAMP)-pattern recognition receptor (PRR) and damage-associated molecular pattern (DAMP)-PRR signaling pathways. We also summarize the application of nanomaterials in the treatment of sepsis. As highlighted here, this strategy could synergistically improve the therapeutic efficacy against both RONS and inflammation in sepsis and may prolong survival. Current challenges and future developments for sepsis treatment are also summarized.

Nanotherapies for sepsis by regulating inflammatory signals and reactive oxygen and nitrogen species: New insight for treating COVID-19.

The complexity of the tumor microenvironment presents significant challenges to cancer therapy, while providing opportunities for targeted drug delivery. Using characteristic signals of the tumor microenvironment, various stimuli-responsive drug delivery systems can be constructed for targeted drug delivery to tumor sites. Among these, the pH is frequently utilized, owing to the pH of the tumor microenvironment being lower than that of blood and healthy tissues. pH-responsive polymer carriers can improve the efficiency of drug delivery in vivo, allow targeted drug delivery, and reduce adverse drug reactions, enabling multifunctional and personalized treatment. pH-responsive polymers have gained increasing interest due to their advantageous properties and potential for applicability in tumor therapy. In this review, recent advances in, and common applications of, pH-responsive polymer nanomaterials for drug delivery in cancer therapy are summarized, with a focus on the different types of pH-responsive polymers. Moreover, the challenges and future applications in this field are prospected.

pH-Responsive Polymer Nanomaterials for Tumor Therapy

Ischemic heart disease (IHD) is the leading cause of disability and mortality worldwide. Reactive oxygen species (ROS) have been shown to play key roles in the progression of diabetes, hypertension, and hypercholesterolemia, which are independent risk factors that lead to atherosclerosis and the development of IHD. Engineered biomaterial‐based nanomedicines are under extensive investigation and exploration, serving as smart and multifunctional nanocarriers for synergistic therapeutic effect. Capitalizing on cell/molecule‐targeting drug delivery, nanomedicines present enhanced specificity and safety with favorable pharmacokinetics and pharmacodynamics. Herein, the roles of ROS in both IHD and its risk factors are discussed, highlighting cardiovascular medications that have antioxidant properties, and summarizing the advantages, properties, and recent achievements of nanomedicines that have ROS scavenging capacity for the treatment of diabetes, hypertension, hypercholesterolemia, atherosclerosis, ischemia/reperfusion, and myocardial infarction. Finally, the current challenges of nanomedicines for ROS‐scavenging treatment of IHD and possible future directions are discussed from a clinical perspective.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/adma.202202169

Yayun Nan

Papers

MoS2-based nanocomposites for cancer diagnosis and therapy

Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries.

Nanotherapies for sepsis by regulating inflammatory signals and reactive oxygen and nitrogen species: New insight for treating COVID-19.