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1.
Advanced Therapeutics ; 6(5) (no pagination), 2023.
Article in English | EMBASE | ID: covidwho-20244710

ABSTRACT

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.

2.
International Journal of Applied Pharmaceutics ; 15(3):1-11, 2023.
Article in English | EMBASE | ID: covidwho-20242785

ABSTRACT

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

3.
Current Materials Science ; 16(4):376-399, 2023.
Article in English | Scopus | ID: covidwho-20242773

ABSTRACT

Nanofibers are a type of nanomaterial with a diameter ranging from ten to a few hundred nanometers with a high surface-to-volume ratio and porosity. They can build a network of high-porosity material with excellent connectivity within the pores, making them a preferred option for numerous applications. This review explores nanofibers from the synthesis techniques to fabricate nanofibers, with an emphasis on the technological applications of nanofibers like water and air filtration, photovoltaics, batteries and fuel cells, gas sensing, photocatalysis, and biomedical applications like wound dressing and drug delivery. The nanofiber production market has an expected compound annual growth rate (CAGR) of 6% and should reach around 26 million US $ in 2026. The limitations and potential opportunities for large-scale applications of nano-fibrous membranes are also discussed. We expect this review could provide enriched information to better understand Electrospun Polymer Nanofiber Technology and recent advances in this field. © 2023 Bentham Science Publishers.

4.
Advances in Nanotechnology for Marine Antifouling ; : 231-270, 2023.
Article in English | Scopus | ID: covidwho-20240941

ABSTRACT

Globally, concerns regarding the COVID-19 pandemic its prevention have become important. Because of COVID-19 and other microbial diseases, enhance research work has emerged revealing new antimicrobial and antiviral materials and techniques. Tremendous growth in nanotechnology has opened up the door to fabricating numerous nanomaterials. These nanomaterials are employed as antimicrobial and antiviral agents for various applications with 99.99% effectiveness compared with conventional techniques. Nanoparticles possess unique physicochemical characteristics for multiple applications. This chapter details the use of nanoparticles for antifungal, antimicrobial, and antiviral applications. It describes various kinds of nanoparticles, such as nanometals, metal oxides, polymeric nanomaterials, and carbon-based nanomaterials. © 2023 Elsevier Inc. All rights reserved.

5.
Critical Reviews in Biomedical Engineering ; 51(1):41-58, 2023.
Article in English | EMBASE | ID: covidwho-20239064

ABSTRACT

The COVID-19 pandemic, emerging/re-emerging infections as well as other non-communicable chronic diseases, highlight the necessity of smart microfluidic point-of-care diagnostic (POC) devices and systems in developing nations as risk factors for infections, severe disease manifestations and poor clinical outcomes are highly represented in these countries. These POC devices are also becoming vital as analytical procedures executable outside of conventional laboratory settings are seen as the future of healthcare delivery. Microfluidics have grown into a revolutionary system to miniaturize chemical and biological experimentation, including disease detection and diagnosis utilizing muPads/paper-based microfluidic devices, polymer-based microfluidic devices and 3-dimensional printed microfluidic devices. Through the development of droplet digital PCR, single-cell RNA sequencing, and next-generation sequencing, microfluidics in their analogous forms have been the leading contributor to the technical advancements in medicine. Microfluidics and machine-learning-based algorithms complement each other with the possibility of scientific exploration, induced by the framework's robustness, as preliminary studies have documented significant achievements in biomedicine, such as sorting, microencapsulation, and automated detection. Despite these milestones and potential applications, the complexity of microfluidic system design, fabrication, and operation has prevented widespread adoption. As previous studies focused on microfluidic devices that can handle molecular diagnostic procedures, researchers must integrate these components with other microsystem processes like data acquisition, data processing, power supply, fluid control, and sample pretreatment to overcome the barriers to smart microfluidic commercialization.Copyright © 2023 by Begell House, Inc.

6.
Advanced Materials Interfaces ; 2023.
Article in English | Web of Science | ID: covidwho-20237000

ABSTRACT

There is a need for rapid, sensitive, specific, and low-cost virus sensors. Recent work has demonstrated that organic electrochemical transistors (OECTs) can detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Here, a simple and low-cost approach to the fabrication of OECT devices with excellent stability and unprecedented sensitivity and specificity for the detection of SARS-CoV-2 virus is demonstrated. The devices rely on the engineered protein minibinder LCB1, which binds strongly to SARS-CoV-2. The resulting devices exhibit excellent sensitivity for the detection of SARS-CoV-2 virus and SARS-CoV-2 spike protein receptor binding domain (RBD). These results demonstrate a simple, effective, and low-cost biomolecular sensor applicable to the real-time detection of SARS-CoV-2 virus and a general strategy for OECT device design that can be applied for the detection of other pathogenic viruses.

7.
Eurasia Journal of Mathematics, Science and Technology Education ; 19(5), 2023.
Article in English | ProQuest Central | ID: covidwho-20231813

ABSTRACT

Online learning should ensure that students' oral communication skills remain good. This study aimed to determine the oral communication skills of chemistry department students in polymer chemistry courses at online learning based on differences in gender and study program. The research design was quantitative descriptive. The data collection tool was an observation sheet about the assessment of oral communication skills collected during presentation activities. The sample was 73 students. Data were analyzed utilizing a one-way analysis of variance test. The findings reveal that students' oral communication skills based on gender have differences, but the difference was not significant. The oral communication skills of male students are higher than female students. There was a significant difference in students' verbal communication skills based on study programs. Chemistry students' oral communication skills have higher than chemistry education students. The implications of the research results are described.

8.
Ieee Transactions on Electron Devices ; 2023.
Article in English | Web of Science | ID: covidwho-2327611

ABSTRACT

Over the past few decades, the field of organic electronics has depicted proliferated growth, due to the advantageous characteristics of organic semiconductors, such as tunability through synthetic chemistry, simplicity in processing, cost-effectiveness, and low-voltage operation, to cite a few. Organic electrochemical transistors (OECTs) have recently emerged as a highly promising technology in the area of biosensing and flexible electronics. OECT-based biosensors are capable of sensing brain activities, tissues, monitoring cells, hormones, DNAs, and glucose. Sensitivity, selectivity, and detection limit are the key parameters adopted for measuring the performance of OECT-based biosensors. This article highlights the advancements and exciting prospects of OECTs for future biosensing applications, such as cell-based biosensing, chemical sensing, DNA/ribonucleic acid (RNA) sensing, glucose sensing, immune sensing, ion sensing, and pH sensing. OECT-based biosensors outperform other conventional biosensors because of their excellent biocompatibility, high transconductance, and mixed electronic-ionic conductivity. At present, OECTs are fabricated and characterized in millimeter and micrometer dimensions, and miniaturizing their dimensions to nanoscale is the key challenge for utilizing them in the field of nanobioelectronics, nanomedicine, and nanobiosensing.

9.
Progress in Chemistry ; 35(3):496-508, 2023.
Article in English | Web of Science | ID: covidwho-2328004

ABSTRACT

With the large-scale spread of COVID-19 around the world, it has caused serious damage to the health of people around the world. In addition to being transmitted by various droplets, viruses can also be transmitted by human touch of contaminated surfaces. However, as a commonly used surface antiviral method, disinfectants have the disadvantage of discontinuously inactivating viruses, which is bad for inhibiting the spread of various infectious viruses. Therefore, it is urgent to protect the surface of daily objects from virus pollution to eliminate the spread of various respiratory viruses ( such as Corona Virus Disease 2019, SARS-CoV-2). From this point of view, it is very important to design and develop effective antiviral coatings. This paper discusses the working mechanisms, performance evaluation methods, processing technologies, practical applications and research progress of nanoparticle antiviral coatings and polymer antiviral coatings for SARS-CoV-2, and also proposes some strategies to design more effective antiviral coatings from the perspective of different types of antiviral coatings. Although some of these antiviral coatings are still in the experimental stage, they still show great potential in the antiviral field.

10.
Journal of Polymer Research ; 30(6), 2023.
Article in English | ProQuest Central | ID: covidwho-2323573

ABSTRACT

Extracorporeal membrane oxygenator (ECMO) is a valuable technology to support people with acute respiratory distress syndrome (ARDS) and is recommended for COVID-19 patients. This study aims to fabricate polymer-based composite membranes coated with ethylcellulose nanoparticles from waste paper and identify the performance of the composite as ECMO candidates. Composite membranes were made from four types of polymers, namely, nylon, PTFE (polytetrafluoroethylene), Pebax® MH-1657, and SBS (poly-(styrene-b-butadiene-b-styrene)). PDMS (polydimethylsiloxane) 1 wt.% and ethylcellulose nanoparticles (3% and 10 wt.%) were used as membrane coatings to increase their hydrophobic properties. The success of cellulose isolation and ethylcellulose synthesis from waste paper was confirmed by the FTIR and XRD analysis. The size of the synthesized ethylcellulose nanoparticles was 32.68 nm. The coating effect on composite membranes was studied by measuring the contact angle, membrane porosity, protein quantification tests, and single gas permeation of O2 and CO2. Based on the protein quantification test, the protein could not pass through the Pebax/PDMS and SBS/PDMS composites coated with 10 wt.% ethylcellulose;this indicated less risk of plasma leakage. The gas permeation test on nylon/PDMS, PTFE/PDMS, and SBS/PDMS composites coated with 10% ethylcellulose resulted high CO2/O2 selectivity, respectively, 2.17, 3.48, and 3.22 as good indication for extracorporeal oxygenation membrane.

11.
ASAIO Journal ; 69(Supplement 1):44, 2023.
Article in English | EMBASE | ID: covidwho-2322466

ABSTRACT

Acquired von Willebrand syndrome (AVWS) contributes to bleeding during extracorporeal membrane oxygenation (ECMO) support. Although it is recognized that AVWS rapidly resolves after ECMO decannulation, this approach may often be clinically unsuitable. In such cases, optimal AVWS management during ECMO support is not well established. We report our approach to managing AVWS in a patient on veno-venous (VV) ECMO for 59 days. A 19-year-old male developed hypoxemic respiratory failure from SARS-CoV-2 pneumonia. Following intubation, he progressed to VV-ECMO support for refractory hypoxemia and was started on bivalirudin for systemic anticoagulation. Two days later, he developed refractory gastrointestinal and oro-nasopharyngeal bleeding despite blood product transfusions and discontinuing bivalirudin. He was started on pantoprazole along with infusions of octreotide and aminocaproic acid. Upper endoscopy on ECMO day 5 revealed an ulcerative bleeding vessel in the duodenum that was clipped. Recurrent mucosal bleeding precluded resumption of systemic anticoagulation. On ECMO day 23, AVWS was diagnosed based on elevated von Willebrand factor (VWF) activity (207%, normal 55-189%) and antigen (234%, normal 50-210%) levels with abnormally low VWF high-molecular-weight multimers. Factor VIII complex was administered twice over the following week. Between doses, the ECMO circuit was exchanged to empirically mitigate suspected shear-related VWF consumption from the fibrin burden, and a repeat endoscopy controlled additional intestinal bleeding with local hemostatic agents. He received 36 units of red blood cells, 2 units of platelets, 2 units of plasma, and 7 pooled units of cryoprecipitate over 31 days leading into these combined interventions. In the 28 days afterwards, he received 3 units of red blood cells, 3.5 pooled units of cryoprecipitate, and no additional platelets or plasma. Our patient was maintained off systemic anticoagulation for 54 of 59 days of VV-ECMO support without any thrombotic complications occurring. With no subsequent clinical evidence of bleeding, repeat VWF testing was done two months post-decannulation and showed near-normal VWF activity (54%) and normal multimer distribution. Our patient rehabilitated well without any neurologic deficits and on discharge was requiring supplemental oxygen with sleep and strenuous activity. Avoiding systemic anticoagulation, repleting VWF, maintaining circuit integrity, and providing local hemostasis, when possible, may be a safe and effective management strategy of AVWS on ECMO support when decannulation is not a viable option.

12.
Smart and Functional Textiles ; : 1-758, 2023.
Article in English | Scopus | ID: covidwho-2321372

ABSTRACT

Smart and Functional Textiles is an application-oriented book covering a wide range of areas from multifunctional nanofinished textiles, coated and laminated textiles, wearable e-textiles, textile-based sensors and actuators, thermoregulating textiles, to smart medical textiles and stimuli-responsive textiles. It also includes chapters on 3D printed smart textiles, automotive smart textiles, smart textiles in military and defense, as well as functional textiles used in care and diagnosis of Covid-19. • Overview of smart textiles and their multidirectional applications • Materials, processes, advanced techniques, design and performance of smart fabrics • Fundamentals, advancements, current challenges and future perspectives of smart textiles. © 2023 Walter de Gruyter GmbH, Berlin/Boston.

13.
Materials Chemistry Frontiers ; 2023.
Article in English | Web of Science | ID: covidwho-2326266

ABSTRACT

Separation membranes play a crucial role in the functioning of artificial organs, such as hemodialysis machines, membrane oxygenators, and artificial liver models. The current COVID-19 pandemic has highlighted the importance of these technologies in the medical community. However, membrane technology in artificial organs faces significant challenges, such as the clearance of low-middle-molecule and protein-bound toxins and limited blood compatibility. In this review, we will discuss the separation mechanisms, separation performance, and biocompatibility of different types of separation membranes used in artificial organs. We will also highlight the opportunities and challenges for next-generation membrane technology in this field, including the need for improved clearance of toxins and increased blood compatibility, as well as the potential for microfluidic devices.

14.
International Journal of Pharmaceutical Sciences and Research ; 14(5):2227-2235, 2023.
Article in English | EMBASE | ID: covidwho-2325091

ABSTRACT

In recent days, the increasing number of microbes and their increasing resistance power against conventional drugs have led to enormous worldwide mortalities, hence they pose a great threat to human health. The modern era is already going through the threat of COVID-19, also caused by one of those microbes called the virus. In order to get a clear understanding, all the microbes have been classified in certain types. Nowadays, to develop new alternative antimicrobial medicines, scientists must acquire clarity about the responsible functional groups of different conventional drugs with proper mechanistic elucidation on different types of microbes. This information not only clarifies the functionalities and properties responsible for exhibiting antimicrobial effects, but also facilitates the idea of new drug development through proper functional group incorporation or modification. These modifications increase the efficacy of antimicrobial drugs as well as their activity and water solubility. In this review, my focus will majorly be on the four main types of microbes and their possible mechanistic elucidation of commonly used antibiotics and alternative antimicrobial medicines discovered till now. I thank the Science and Engineering Research Board (SERB), Council of Scientific and Industrial Research (CSIR), and Government of India for my fellowship and research grants during my Ph.D in Indian Institute of Science Education and Research, Kolkata and Postdoctoral journey in the University of Burdwan. I acknowledge Prof. Bimalendu Ray (Chemistry department, The University of Burdwan), Prof. Priyadarsi De, (Polymer Research Centre, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata), Prof. Punyasloke Bhadury (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata), Dr. Anwesha Ghosh (Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata) for many helpful discussions and laboratory use.Copyright © 2023 are reserved by International Journal of Pharmaceutical Sciences and Research.

15.
Pharm Nanotechnol ; 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2321997

ABSTRACT

Viral diseases are one of the major causes of mortality worldwide. The emergence of pandemics because of the Covid virus creates a dire need for an efficient mechanism to combat the disease. Viruses differ from other pathogenic infections; they render the host immune system vulnerable. One of the major challenges for developing antivirals is the resistance developed by the overuse of drugs, which is inevitable as most viral diseases require a large number of doses. Viral infection detection, prevention, and treatment have significantly benefitted from developing several innovative technologies in recent years. Nanotechnology has emerged as one of the most promising technologies because of its capacity to deal with viral infections efficiently and eradicate the lagging of conventional antiviral drugs. This review briefly presents an overview of the application of nanotechnology for viral therapy.

16.
Stem Cell Res Ther ; 14(1): 112, 2023 04 27.
Article in English | MEDLINE | ID: covidwho-2323672

ABSTRACT

Cell therapy is an accessible method for curing damaged organs or tissues. Yet, this approach is limited by the delivery efficiency of cell suspension injection. Over recent years, biological scaffolds have emerged as carriers of delivering therapeutic cells to the target sites. Although they can be regarded as revolutionary research output and promote the development of tissue engineering, the defect of biological scaffolds in repairing cell-dense tissues is apparent. Cell sheet engineering (CSE) is a novel technique that supports enzyme-free cell detachment in the shape of a sheet-like structure. Compared with the traditional method of enzymatic digestion, products harvested by this technique retain extracellular matrix (ECM) secreted by cells as well as cell-matrix and intercellular junctions established during in vitro culture. Herein, we discussed the current status and recent progress of CSE in basic research and clinical application by reviewing relevant articles that have been published, hoping to provide a reference for the development of CSE in the field of stem cells and regenerative medicine.


Subject(s)
Regenerative Medicine , Tissue Engineering , Regenerative Medicine/methods , Tissue Engineering/methods , Cell Engineering , Stem Cells , Cell- and Tissue-Based Therapy , Extracellular Matrix , Tissue Scaffolds
17.
Journal of Cystic Fibrosis ; 21(Supplement 2):S339, 2022.
Article in English | EMBASE | ID: covidwho-2315958

ABSTRACT

Background: Next-generation SARS-CoV-2 vaccines demonstrated that nanoparticle messenger ribonucleic acid (mRNA) delivery is effective and safe for in vivo delivery in humans. Current treatments for cystic fibrosis (CF) primarily focus on modulator drug therapies designed to correct malfunctioning CF transmembrane conductance regulator (CFTR) protein, but these modulators are ineffective for the 10% of people with CF with variants that do not allow protein production. Among these is the splice variant 3120 + 1G >A, the most common CF-causing mutation in native Africans. Gene editing would allow production of CFTR protein and enhancement of function using available CFTR modulators. We have demonstrated that electroporation of a modified CRISPR-Cas9 base editor to primary human bronchial epithelial cells carrying 3120 + 1G >A and F508del mutant alleles achieved 75% genome editing of the splice variant, resulting in approximately 40% wild-type (WT) CFTR function [1]. Here,we evaluate the effectiveness of several new nanoparticle formulations at delivering green fluorescent protein (GFP) mRNA to CF bronchial epithelial (CFBE41o-) cells. Using the optimal formulation,we then tested the efficacy correction of the 3120 + 1G >Avariant in a CFTR expression minigene (EMG) integrated into the genome of isogenic CFBE cells using mRNA and plasmid deoxyribonucleic acid (DNA) encoding adenine base editor (ABE) and guide (g)RNA. Method(s): GFP served as a reporter to evaluate transfection efficiency, cell viability, and mean fluorescence intensity (MFI) for three dosages (150, 75, 32.5 ng of mRNA), four polymer-to-mRNA to weight (w/w) ratios (60, 40, 30, 20), and four polymers (R, Y, G, B). 7-AAD served as a live/dead stain to quantify viability, with flow cytometry results analyzed using FlowJo software. CFBE cells stably expressing the 3120 + 1G >A EMG were transfected with the optimized nanoparticle formulation to deliver ABE and gRNA at two dosages (150, 75 ng) of mRNA and DNA. CFTR function in CFBE cellswas measured by short circuit current, forskolin stimulation, and inh-172 inhibition as a measure of editing efficiency. Result(s): Flow cytometry showed that polymer R achieved more than 85% GFP transfection, compared with a maximum of approximately 35% for the other three polymers at the maximum 150-ng dose, with approximately 80% viability normalized to untreated cells. In addition, polymer R achieved GFP MFI more than one order of magnitude as high as other formulations (~30 000 vs 2700 MFI) for the other three polymers at 150-ng dose and 40 w/w ratio. CFBE cells transfected with polymer R nanoparticles containing ABE and guide RNA at 75 ng and 150 ng showed mean CFTR function increase to 10 muA 6 (standard error of the mean [SEM] 1.1 muA) (~10% of WT) and 6.3 muA (SEM 0.9 muA) (~6% of WT), respectively. Greater toxicity at the higher dose could explain the larger increase in CFTR current at the lower dose. DNA-encoded ABE plasmid and gRNA showed a less robust increase in CFTR function (2.9 muA [SEM 0.4 muA] for 75-ng dose;3.0 muA [SEM 0.4 muA] for 150-ng dose), which was probably a result of the nanoparticle formulation being optimized for RNA instead of DNA cargo or the additional intracellular barriers that must be overcome for successful DNA delivery. Conclusion(s): We demonstrated that an optimized nanoparticle formulation containing ABE and gRNA can correct splicing of isogenic cells bearing the 3120 + 1G >A CFTR variant, resulting in recovery of CFTR function. In ongoing work, we are adapting these nanoparticles for RNA- and DNAencoded ABE and gRNA delivery to primary human bronchial epithelial cells.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

18.
Talanta ; 263: 124678, 2023 Oct 01.
Article in English | MEDLINE | ID: covidwho-2320337

ABSTRACT

As a common antioxidant and nutritional fortifier in food chemistry, rutin has positive therapeutic effects against novel coronaviruses. Here, Ce-doped poly(3,4-ethylenedioxythiophene) (Ce-PEDOT) nanocomposites derived through cerium-based metal-organic framework (Ce-MOF) as a sacrificial template have been synthesized and successfully applied to electrochemical sensors. Due to the outstanding electrical conductivity of PEDOT and the high catalytic activity of Ce, the nanocomposites were used for the detection of rutin. The Ce-PEDOT/GCE sensor detects rutin over a linear range of 0.02-9 µM with the limit of detection of 14.7 nM (S/N = 3). Satisfactory results were obtained in the determination of rutin in natural food samples (buckwheat tea and orange). Moreover, the redox mechanism and electrochemical reaction sites of rutin were investigated by the CV curves of scan rate and density functional theory. This work is the first to demonstrate the combined PEDOT and Ce-MOF-derived materials as an electrochemical sensor to detect rutin, thus opening a new window for the application of the material in detection.


Subject(s)
Cerium , Metal-Organic Frameworks , Rutin , Polymers , Electrochemical Techniques/methods
19.
Angew Chem Int Ed Engl ; 62(29): e202304010, 2023 07 17.
Article in English | MEDLINE | ID: covidwho-2312956

ABSTRACT

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram-scale with high molecular weight (MW=450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT polymerization. Cryo-electron tomography (Cryo-ET) analysis of MIP-1 confirmed a mucin-mimetic wormlike single-chain fiber structure (length=144±59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS-CoV-2 and its mutant strain, with a remarkable low half maximal (IC50 ) inhibitory concentration (IC50 =10.0 nM). Additionally, we investigate the impact of fiber length on SARS-CoV-2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths.


Subject(s)
COVID-19 , Molecular Imprinting , Humans , Mucins , SARS-CoV-2 , Polymers/pharmacology , Polymers/chemistry , Molecular Imprinting/methods
20.
Mol Ther Nucleic Acids ; 32: 743-757, 2023 Jun 13.
Article in English | MEDLINE | ID: covidwho-2307965

ABSTRACT

Genetic immunization is an attractive approach for prophylactic and therapeutic vaccination using synthetic vectors to deliver antigen-encoding nucleic acids. Recently, DNA delivered by a physical means or RNA by liposomes consisting of four different lipids demonstrated good protection in human phase III clinical trials and received Drugs Controller General of India and US FDA approval to protect against COVID-19, respectively. However, the development of a system allowing for efficient and simple delivery of nucleic acids while improving immune response priming has the potential to unleash the full therapeutic potential of genetic immunization. DNA-based gene therapies and vaccines have the potential for rapid development, as exemplified by the recent approval of Collategene, a gene therapy to treat human critical limb ischemia, and ZyCoV, a DNA vaccine delivered by spring-powered jet injector to protect against SARS-CoV2 infection. Recently, we reported amphiphilic block copolymer 704 as a promising synthetic vector for DNA vaccination in various models of human diseases. This vector allows dose sparing of antigen-encoding plasmid DNA. Here, we report the capacity of 704-mediated HIV and anti-hepatocellular carcinoma DNA vaccines to induce the production of specific antibodies against gp120 HIV envelope proteins in mice and against alpha-fetoprotein antigen in non-human primates, respectively. An investigation of the underlying mechanisms showed that 704-mediated vaccination did trigger a strong immune response by (1) allowing a direct DNA delivery into the cytosol, (2) promoting an intracytoplasmic DNA sensing leading to both interferon and NF-κB cascade stimulation, and (3) inducing antigen expression by muscle cells and presentation by antigen-presenting cells, leading to the induction of a robust adaptive response. Overall, our findings suggest that the 704-mediated DNA vaccination platform is an attractive method to develop both prophylactic and therapeutic vaccines.

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