An ultrasensitive electrochemiluminescence immunosensor for SARS-CoV-2 nucleocapsid protein detection based on signal amplification strategy of DMSN@QDs

Based on signal amplification strategy of dendritic mesoporous silica nanospheres loaded with CdSe/ZnS quantum dots (DMSN@QDs), an ultrasensitive electrochemiluminescence (ECL) immunosensor with magnetic separation was constructed for the detection of SARS-CoV-2 nucleocapsid protein (NP). DMSN, a mesoporous material with abundant radial pores, large specific surface area and high porosity, can increase the loading capacity of QDs and hinder their aggregation as the nanocarrier. DMSN@QDs with good ECL efficiency were used as signal labels to construct a sandwich immunosensor. The designed ECL immunosensor displayed a good linear relationship for NP concentrations ranging from 0.005 ng mL(-1) to 50 ng mL(-1), with a limit of detection of 3.33 pg mL(-1). The ECL immunosensor was successfully applied to detect NP in human serum samples with satisfactory recovery. This strategy provided a new method for detecting NP and expanded the application field of DMSN.

STING agonist-loaded mesoporous manganese-silica nanoparticles for vaccine applications.

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2. MnOx@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnOx@HMSN(CDA) amplified the activation of the STING pathway and enhanced the production of type-I interferons and other proinflammatory cytokines from dendritic cells. MnOx@HMSN(CDA) carrying cancer neoantigens elicited robust antitumor T-cell immunity with therapeutic efficacy in two different murine tumor models. Furthermore, MnOx@HMSN(CDA) loaded with SARS-CoV-2 antigen achieved strong and durable (up to one year) humoral immune responses with neutralizing capability. These results demonstrate that MnOx@HMSN(CDA) is a versatile nanoplatform for vaccine applications.

Recent Advances in the Use of Mesoporous Silica Nanoparticles for the Diagnosis of Bacterial Infections.

Public awareness of infectious diseases has increased in recent months, not only due to the current COVID-19 outbreak but also because of antimicrobial resistance (AMR) being declared a top-10 global health threat by the World Health Organization (WHO) in 2019. These global issues have spiked the realization that new and more efficient methods and approaches are urgently required to efficiently combat and overcome the failures in the diagnosis and therapy of infectious disease. This holds true not only for current diseases, but we should also have enough readiness to fight the unforeseen diseases so as to avoid future pandemics. A paradigm shift is needed, not only in infection treatment, but also diagnostic practices, to overcome the potential failures associated with early diagnosis stages, leading to unnecessary and inefficient treatments, while simultaneously promoting AMR. With the development of nanotechnology, nanomaterials fabricated as multifunctional nano-platforms for antibacterial therapeutics, diagnostics, or both (known as "theranostics") have attracted increasing attention. In the research field of nanomedicine, mesoporous silica nanoparticles (MSN) with a tailored structure, large surface area, high loading capacity, abundant chemical versatility, and acceptable biocompatibility, have shown great potential to integrate the desired functions for diagnosis of bacterial infections. The focus of this review is to present the advances in mesoporous materials in the form of nanoparticles (NPs) or composites that can easily and flexibly accommodate dual or multifunctional capabilities of separation, identification and tracking performed during the diagnosis of infectious diseases together with the inspiring NP designs in diagnosis of bacterial infections.

Targeted-lung delivery of dexamethasone using gated mesoporous silica nanoparticles. A new therapeutic approach for acute lung injury treatment.

Acute lung injury (ALI) is a critical inflammatory syndrome, characterized by increased diffuse inflammation and severe lung damage, which represents a clinical concern due to the high morbidity and mortality in critical patients. In last years, there has been a need to develop more effective treatments for ALI, and targeted drug delivery to inflamed lungs has become an attractive research field. Here, we present a nanodevice based on mesoporous silica nanoparticles loaded with dexamethasone (a glucocorticoid extensively used for ALI treatment) and capped with a peptide that targets the TNFR1 receptor expressed in pro-inflammatory macrophages (TNFR-Dex-MSNs) and avoids cargo leakage. TNFR-Dex-MSNs nanoparticles are preferentially internalized by pro-inflammatory macrophages, which overexpressed the TNFR1 receptor, with the subsequent cargo release upon the enzymatic hydrolysis of the capping peptide in lysosomes. Moreover, TNFR-Dex-MSNs are able to reduce the levels of TNF-α and IL-1ß cytokines in activated pro-inflammatory M1 macrophages. The anti-inflammatory effect of TNFR-Dex-MSNs is also tested in an in vivo ALI mice model. The administered nanodevice (intravenously by tail vein injection) accumulated in the injured lungs and the controlled dexamethasone release reduces markedly the inflammatory response (TNF-α IL-6 and IL-1ß levels). The attenuation in lung damage, after treatment with TNFR-Dex-MSNs, is also confirmed by histopathological studies. Besides, the targeted-lung dexamethasone delivery results in a decrease of dexamethasone derived side-effects, suggesting that targeted nanoparticles can be used for therapy in ALI and could help to overcome the clinical limitations of current treatments.