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.

Antioxidating and reinforcing effect of polydopamine functionalized silica on natural rubber latex films

Since the outbreak of COVID-19, the demand for natural latex products with increased mechanical properties and aging resistance has surged. Based on the excellent adhesion and antioxidant properties of polydopamine (PDA), we employed a one-pot method to modify the surface of silica substrates using PDA containing a polyphenol structure, to prepare a reinforced silica-PDA composite latex material with antioxidant properties. As expected, the silica-PDA composite achieved both uniform dispersion and good interfacial interactions with natural rubber latex (NRL). In addition, compared with common NRL/silica films, the mechanical properties of the NRL/silica-PDA film were significantly improved;specifically, silica-PDA can highly-enhanced the mechanical property of NRL film from 24.94 to 32.18 MPa of tensile strength. Further, the antioxidant activity of the silica-PDA film exceeded that of commercially available antioxidant D. Considering the notable performance boost of silica-PDA composites on NRL films, we believe that the treatment of silica with natural polyphenols offers a convenient and facile new route for the preparation of environmentally friendly multifunctional silica additives. © 2023 Wiley Periodicals LLC.

Amino-terminated hyperbranched polymer functionalized graphene oxide with in situ trapped silver nanoparticles for high-performance antibacterial nonwoven fabric

Antibacterial fabric with high thermal stability and mechanical strength is important for personalized protection, especially under the background of coronavirus pandemic (COVID-19). This paper presents a facile approach toward high-efficient antibacterial polypropylene spunbonded nonwoven fabrics (SNFs), which are decorated by a composite of graphene oxide embedded with silver nanoparticles (AgNPs/GO) through dip-coating and in situ reduction effect of pre-introduced amino-terminated hyperbranched polymer (HBP-NH2). Typically, HBP-NH2 was grafted onto the GO nanosheets, then silver ions were trapped and self-reduced by the HBP-NH2 to generate silver nanoparticles decorated GO. The produced AgNPs are uniformly dispersed on the GO with a size of 13 nm. As an antibacterial coating, the Ag/GO composite could tightly wrap the SNFs fibers through the dip-padding method, capable of enhancing the thermal stability and mechanical property of SNFs. The treated SNFs exhibited excellent antibacterial activities (~99.9%) against both Echerisia coli and Staphylococcus aureus, promising important potential for biomedical and personal protection applications. © 2022 Wiley Periodicals LLC.

Porphyrinoids coated Silica Nanoparticles Capacitive Sensors for COVID-19 Detection from the Analysis of Blood Serum Volatolome

The growing interest in analyzing human volatolome is among the primary motivations for developing gas sensors. Among the available sensor technologies, porphyrinoids coated quartz microbalance (QMBs) sensors demonstrate to be sensitive and selective enough to identify several diseases. Some drawbacks affect these transducers, such as difficult miniaturization and low-cost production. In this paper, we investigate capacitive sensors based on films of porphyrinoids functionalized silica nanoparticles as alternative and advantageous technology to match the performance of quartz microbalance sensors. The variation of sensor capacitance depended on the diffusion of airborne molecules into the sensing film, favoring the extraction of low-correlated dynamic features. As a demonstration of sensor properties, a three-sensor array has been used to measure the volatile compounds from blood serum to discriminate COVID-19 over other pathologies. Sensor data, processed by linear discriminant analysis, identified COVID-19 samples with 89% and 75% accuracy in training and test.

Highly Sensitive and Selective Sensing Probe for Determination of Anti-Covid-19 Remdesvir: Application to Pharmaceutical Dosage Form and Biological Fluids

We reported the first investigational electrochemical study for Remdesvir (REM). REM is a promising antiviral agent used recently for the treatment of the most dangerous pandemic disease nowadays (COVID-19). Anionic surfactant, silica nanoparticles, and multiwall carbon nanotubes modified carbon paste (SDS/SiO2/MWCNT/CPE) sensor was designed to introduce our approach. The results revealed irreversible diffusion oxidative reaction of REM with two well-defined peaks (E1/V = 1.19, E2/V = 1.35) in 0.1 M phosphate buffer of pH 6 using differential pulse (DP) voltammetry. A linear relationship between the peak current and the drug concentration was established over the concentration range of 1.66 × 10-7-3.52 × 10-6 M (100-200 ng ml-1) with a limit of detection (LOD) of 4.80 × 10-8 M and limit of quantitation (LOQ) of 8.0 × 10-8 M and mean % recovery ± % RSD of 99.05 ± 1.94. The proposed method succeeded in the determination of the drug in its pharmaceutical dosage form, in human plasma with and human urine samples. Finally, the method was validated according to ICH guidelines and FDA guidance for the determination of the drug in biological fluids. The developed data was found to be in good agreement with a validated reported method. © 2022 The Electrochemical Society ("ECS").

APTES-Based Silica Nanoparticles as a Potential Modifier for the Selective Sequestration of CO2 Gas Molecules.

In this work, we have described the characterization of hybrid silica nanoparticles of 50 nm size, showing outstanding size homogeneity, a large surface area, and remarkable CO2 sorption/desorption capabilities. A wide battery of techniques was conducted ranging from spectroscopies such as: UV-Vis and IR, to microscopies (SEM, AFM) and CO2 sorption/desorption isotherms, thus with the purpose of the full characterization of the material. The bare SiO2 (50 nm) nanoparticles modified with 3-aminopropyl (triethoxysilane), APTES@SiO2 (50 nm), show a remarkable CO2 sequestration enhancement compared to the pristine material (0.57 vs. 0.80 mmol/g respectively at 50 °C). Furthermore, when comparing them to their 200 nm size counterparts (SiO2 (200 nm) and APTES@SiO2 (200 nm)), there is a marked CO2 capture increment as a consequence of their significantly larger micropore volume (0.25 cm3/g). Additionally, ideal absorbed solution theory (IAST) was conducted to determine the CO2/N2 selectivity at 25 and 50 °C of the four materials of study, which turned out to be >70, being in the range of performance of the most efficient microporous materials reported to date, even surpassing those based on silica.

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.

Structural Alterations of Antigens at the Material Interface: An Early Decision Toolbox Facilitating Safe-by-Design Nanovaccine Development.

Nanomaterials have found extensive interest in the development of novel vaccines, as adjuvants and/or carriers in vaccination platforms. Conjugation of protein antigens at the particle surface by non-covalent adsorption is the most widely used approach in licensed particulate vaccines. Hence, it is essential to understand proteins' structural integrity at the material interface in order to develop safe-by-design nanovaccines. In this study, we utilized two model proteins, the wild-type allergen Bet v 1 and its hypoallergenic fold variant (BM4), to compare SiO2 nanoparticles with Alhydrogel® as particulate systems. A set of biophysical and functional assays including circular dichroism spectroscopy and proteolytic degradation was used to examine the antigens' structural integrity at the material interface. Conjugation of both biomolecules to the particulate systems decreased their proteolytic stability. However, we observed qualitative and quantitative differences in antigen processing concomitant with differences in their fold stability. These changes further led to an alteration in IgE epitope recognition. Here, we propose a toolbox of biophysical and functional in vitro assays for the suitability assessment of nanomaterials in the early stages of vaccine development. These tools will aid in safe-by-design innovations and allow fine-tuning the properties of nanoparticle candidates to shape a specific immune response.

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.

Modelling the adsorption of proteins to nanoparticles at the solid-liquid interface.

HYPOTHESIS: We developed a geometrical model to determine the theoretical maximum number of proteins that can pack as a monolayer surrounding a spherical nanoparticle. We applied our new model to study the adsorption of receptor binding domain (RBD) of the SARS-CoV-2 spike protein to silica nanoparticles. Due to its abundance and extensive use in manufacturing, silica represents a reservoir where the virus can accumulate. It is therefore important to study the adsorption and the persistence of viral components on inanimate surfaces. EXPERIMENTS: We used previously published datasets of nanoparticle-adsorbed proteins to validate the new model. We then used integrated experimental methods and Molecular Dynamics (MD) simulations to characterise binding of the RBD to silica nanoparticles and the effect of such binding on RBD structure. FINDINGS: The new model showed excellent fit with existing datasets and, combined to new RBD-silica nanoparticles binding data, revealed a surface occupancy of 32% with respect to the maximum RBD packing theoretically achievable. Up to 25% of RBD's secondary structures undergo conformational changes as a consequence of adsorption onto silica nanoparticles. Our findings will help developing a better understanding of the principles governing interaction of proteins with surfaces and can contribute to control the spread of SARS-CoV-2 through contaminated objects.

Plant-derived silica nanoparticles and composites for biosensors, bioimaging, drug delivery and supercapacitors: a review.

Silica nanoparticles have rapidly found applications in medicine, supercapacitors, batteries, optical fibers and concrete materials, because silica nanoparticles have tunable physical, chemical, optical and mechanical properties. In most applications, high-purity silica comes from synthetic organic precursors, yet this approach could be costly, polluting and non-biocompatible. Alternatively, natural silica sources from biomass are often cheap and abundant, yet they contain impurities. Silica can be extracted from corn cob, coffee husk, rice husk, sugarcane bagasse and wheat husk wastes, which are often disposed of in rivers, lands and ponds. These wastes can be used to prepare homogenous silica nanoparticles. Here we review properties, preparation and applications of silica nanoparticles. Preparation includes chemical and biomass methods. Applications include biosensors, bioimaging, drug delivery and supercapacitors. In particular, to fight the COVID-19 pandemic, recent research has shown that silver nanocluster/silica deposited on a mask reduces SARS-Cov-2 infectivity to zero.

Can nanotechnology help in the fight against COVID-19?

INTRODUCTION: The current COVID-19 pandemic caused by the SARS-CoV-2 virus demands the development of strategies not only to detect or inactivate the virus, but to treat it (therapeutically and prophylactically). COVID-19 is not only a critical threat for the population with risk factors, but also generates a dramatic economic impact in terms of morbidity and the overall interruption of economic activities. AREAS COVERED: Advanced materials are the basis of several technologies that could diminish the impact of COVID-19: biosensors might allow early virus detection, nanosized vaccines are powerful agents that could prevent viral infections, and nanosystems with antiviral activity could bind the virus for inactivation or destruction upon application of an external stimulus. Herein all these methods are discussed under the light of cutting-edge technologies and the previously reported prototypes targeting enveloped viruses similar to SARS-CoV-2. This analysis was derived from an extensive scientific literature search (including pubmed) performed on April 2020. EXPERT OPINION: Perspectives on how biosensors, vaccines, and antiviral nanosystems can be implemented to fight COVID-19 are envisioned; identifying the approaches that can be implemented in the short term and those that deserve long term research to cope with respiratory viruses-related pandemics in the future.