Tumor microenvironment-responsive gold nanodendrites for nanoprobe-based single-cell Raman imaging and tumor-targeted chemo-photothermal therapy

Nanodendrite particles (NDs) with densely branched structures and biomimetic architectures have exhibited great promise in tumor therapy owing to their prolonged in vivo circulation time and exceptional photothermal efficiency. Nevertheless, traditional NDs are deficient in terms of specific surface modification and targeting tumors, which restricts their potential for broader clinical applications. Here, we developed coronavirus-like gold NDs through a seed-mediated approach and using silk fibroin (SF) as a capping agent. Our results demonstrate that these NDs have a favorable drug-loading capacity (∼65.25%) and light-triggered release characteristics of doxorubicin hydrochloride (DOX). Additionally, NDs functionalized with specific probes exhibited exceptional surface-enhanced Raman scattering (SERS) characteristics, enabling high-sensitivity Raman imaging of unstained single cells. Moreover, these NDs allowed for real-time monitoring of endocytic NDs for over 24 h. Furthermore, ND@DOX conjugated with tumor-targeting peptides exhibited mild hyperthermia, minimal cytotoxicity, and effective targeting towards cancer cells in vitro, as well as responsiveness to the tumor microenvironment (TME) in vivo. These unique properties led to the highest level of synergistic tumor-killing efficiency when stimulated by a near-infrared (NIR) laser at 808 nm. Therefore, our virus-like ND functionalized with SF presents a novel type of nanocarrier that exhibits significant potential for synergistic applications in precision medicine.

Effect of continuing the use of renin-angiotensin system inhibitors on mortality in patients hospitalized for coronavirus disease 2019: a systematic review, meta-analysis, and meta-regression analysis.

BACKGROUND: The effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on mortality was preliminarily explored through the comparison of ACEIs/ARBs with non-ACEIs/ARBs in patients with coronavirus disease 2019 (COVID-19). Reaching a conclusion on whether previous ACEI/ARB treatment should be continued in view of the different ACE2 levels in the comparison groups was not unimpeachable. Therefore, this study aimed to further elucidate the effect of ACEI/ARB continuation on hospital mortality, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) in the same patient population. METHODS: We searched PubMed, the Cochrane Library, Ovid, and Embase for relevant articles published between December 1, 2019 and April 30, 2022. Continuation of ACEI/ARB use after hospitalization due to COVID-19 was considered as an exposure and discontinuation of ACEI/ARB considered as a control. The primary outcome was hospital mortality, and the secondary outcomes included 30-day mortality, rate of ICU admission, IMV, and other clinical outcomes. RESULTS: Seven observational studies and four randomized controlled trials involving 2823 patients were included. The pooled hospital mortality in the continuation group (13.04%, 158/1212) was significantly lower than that (22.15%, 278/1255) in the discontinuation group (risk ratio [RR] = 0.45; 95% confidence interval [CI], 0.28-0.72; P = 0.001). Continuation of ACEI/ARB use was associated with lower rates of ICU admission (10.5% versus 16.2%, RR = 0.63; 95% CI 0.5-0.79; P < 0.0001) and IMV (8.2% versus 12.5%, RR = 0.62; 95% CI 0.46-0.83, P = 0.001). Nevertheless, the effect was mainly demonstrated in the observational study subgroup (P < 0.05). Continuing ACEI/ARB had no significant effect on 30-day mortality (P = 0.34), acute myocardial infarction (P = 0.08), heart failure (P = 0.82), and acute kidney injury after hospitalization (P = 0.98). CONCLUSION: Previous ACEI/ARB treatment could be continued since it was associated with lower hospital deaths, ICU admission, and IMV in patients with COVID-19, although the benefits of continuing use were mainly shown in observational studies. More evidence from multicenter RCTs are still needed to increase the robustness of the data. Trial registration PROSPERO (CRD42022341169). Registered 27 June 2022.

Back Cover: Detection, prevention and treatment of COVID-19 and opportunities for nanobiotechnology (View 4/2022)

In article number 20200181, Chuanbin Mao, Mingying Yang and their co-wokers have demonstrated that nanobiotechnology holds promise for combating COVID-19. It provides nanoscale probes to detect COVID-19, nanoscale vaccines to prevent COVID-19, and nanoscale therapeutics to treat COVID-19. Because nanoparticles are comparable to the virus particles that cause COVID-19, the nanoparticles can be engineered to detect, prevent or treat COVID-19 in a more efficient manner than the other agents.

Detection, prevention and treatment of COVID-19 and opportunities for nanobiotechnology.

Since the outbreak of COVID-19, the number of confirmed cases and deaths has increased globally at a dramatic speed. In view of the serious health threat to humans, this review discusses the state-of-the-art studies about fighting this disease. It summarizes the current strategies and recent advances in detecting, preventing, and treating COVID-19 and interprets the underlying mechanisms in detail. Detection of COVID-19 can be successfully achieved by multiple techniques such as polymerase chain reaction, computed tomography imaging, and nano-biosensing. Inactivated virus vaccine, nucleic acid vaccine, and different nanoparticles have been employed to effectively prevent COVID-19. A variety of agents such as antiviral agents, neutralizing antibodies, and nanotherapeutics have been developed to treat COVID-19 with exciting efficacy. Although nanobiotechnology has shown great potential in the diagnosis, prevention, and treatment of COVID-19, efforts should be made to explore new biocompatible nano-biomaterials to advance this field to clinical applications. Hence, nanobiotechnology paves a new way to detect, prevent, and treat COVID-19 effectively.

Serum levels of the IgA isotype switch factor TGF-ß1 are elevated in patients with COVID-19.

We previously observed enhanced immunoglobulin A (IgA) responses in severe COVID-19, which might confer damaging effects. Given the important role of IgA in immune and inflammatory responses, the aim of this study was to investigate the dynamic response of the IgA isotype switch factor TGF-ß1 in COVID-19 patients. We observed, in a total of 153 COVID-19 patients, that the serum levels of TGF-ß1 were increased significantly at the early and middle stages of COVID-19, and correlated with the levels of SARS-CoV-2-specific IgA, as well as with the APACHE II score in patients with severe disease. In view of the genetic association of the TGF-ß1 activator THBS3 with severe COVID-19 identified by the COVID-19 Host Genetics Initiative, this study suggests TGF-ß1 may play a key role in COVID-19.

Multiplexed analysis of circulating IgA antibodies for SARS-CoV-2 and common respiratory pathogens in COVID-19 patients.

Previous studies have revealed a diagnostic role of pathogen-specific IgA in respiratory infections. However, co-detection of serum specific IgA for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and common respiratory pathogens remains largely unexplored. This study utilizes a protein microarray technology for simultaneous and quantitative measurements of specific IgAs for eight different respiratory pathogens including adenovirus, respiratory syncytial virus, influenza virus type A, influenza virus type B, parainfluenza virus, mycoplasma pneumoniae, chlamydia pneumoniae, and SARS-CoV-2 in serum sample of patients with coronavirus disease 2019 (COVID-19). A total of 42 patients with COVID-19 were included and categorized into severe cases (20 cases) and nonsevere cases (22 cases). The results showed that co-detection rate of specific-IgA for SARS-CoV-2 with at least one pathogen were significantly higher in severe cases than that of nonsevere cases (72.2% vs. 46.2%, p = .014). Our study indicates that co-detection of IgA antibodies for respiratory pathogens might provide diagnostic value for the clinics and also be informative for risk stratification and disease management in patients with COVID-19.