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Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.
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Influenza outbreaks are a major burden worldwide annually. While seasonal vaccines do provide protection against infection, they are limited in that they need to be updated every year to account for the constantly mutating virus. Recently, lipid nanoparticles (LNPs) encapsulating mRNA have seen major success as a vaccine platform for SARS-CoV-2. Herein, we applied LNPs to deliver an mRNA encoding a computationally optimized broadly active (COBRA) influenza immunogen. These COBRA mRNA LNPs induced a broadly active neutralizing antibody response and protection after lethal influenza challenge. To further increase the immunogenicity of the COBRA mRNA LNPs, we combined them with acetalated dextran microparticles encapsulating a STING agonist. Contrary to recent findings, the STING agonist decreased the immunogenicity of the COBRA mRNA LNPs which was likely due to a decrease in mRNA translation as shown in vitro. Overall, this work aids in future selection of adjuvants to use with mRNA LNP vaccines.
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Vacinas contra Influenza , Nanovacinas , Nucleotídeos Cíclicos , Animais , Feminino , Camundongos , Adjuvantes Imunológicos/administração & dosagem , Anticorpos Neutralizantes/imunologia , Dextranos/química , Dextranos/administração & dosagem , Imunogenicidade da Vacina , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Lipídeos/química , Lipídeos/administração & dosagem , Lipossomos , Camundongos Endogâmicos BALB C , Vacinas de mRNA , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanovacinas/administração & dosagem , Nanovacinas/química , Nucleotídeos Cíclicos/administração & dosagem , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Polímeros/química , Polímeros/administração & dosagem , RNA Mensageiro/administração & dosagem , RNA Mensageiro/imunologiaRESUMO
Natural organisms have evolved multi-scale wet gas sensing interfaces with optimized mass transport pathways in biological fluid environments, which sheds light on developing artificial counterparts with improved wet gas sensing abilities and practical applications. Herein, we highlighted current advances in wet gas sensing taking advantage of optimized mass transport pathways endowed by multi-scale interface design. Common moisture resistance (e.g., employing moisture resistant sensing materials, post-modifying moisture resistant coatings, physical heating for moisture resistance, and self-removing hydroxyl groups) and moisture absorption (e.g., employing moisture absorption sensing materials and post-modifying moisture absorption coatings) strategies for wet gas sensing were discussed. Then, the design principles of bioinspired multi-scale wet gas sensing interfaces were provided, including macro-level condensation mediation, micro/nano-level transport pathway adjustment and molecular level moisture-proof design. Finally, perspectives on constructing bioinspired multi-scale wet gas sensing interfaces were presented, which will not only deepen our understanding of the underlying principles, but also promote practical applications.
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Messenger RNA (mRNA) delivery platforms often facilitate protein expression in the liver following intravenous injection and have been optimized for use in normally oxygenated cells (21% O2 atmosphere). However, there is a growing need for mRNA therapy in diseases affecting non-liver organs, such as the lungs. Additionally, many diseases are characterized by hypoxia (<21% O2 atmosphere), a state of abnormally low oxygenation in cells and tissues that can reduce the efficacy of mRNA therapies by upwards of 80%. Here, we report a Tunable Lung-Expressing Nanoparticle Platform (TULEP) for mRNA delivery, whose properties can be readily tuned for optimal expression in hypoxic environments. Briefly, our study begins with the synthesis and characterization of a novel amino acrylate polymer that can be effectively complexed with mRNA payloads into TULEPs. We study the efficacy and mechanism of mRNA delivery using TULEP, including analysis of the cellular association, endocytosis mechanisms, endosomal escape, and protein expression in a lung cell line. We then evaluate TULEP under hypoxic conditions and address hypoxia-related deficits in efficacy by making our system tunable with adenosine triphosphate (ATP). Finally, we conclude our study with an in vivo analysis of mRNA expression, biodistribution, and tolerability of the TULEP platform in mice. In presenting these data, we hope that our work highlights the utility of TULEPs for tunable and effective mRNA delivery while more broadly highlighting the utility of considering oxygen levels when developing mRNA delivery platforms.
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Pulmão , RNA Mensageiro , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/administração & dosagem , Pulmão/metabolismo , Humanos , Animais , Camundongos , Nanopartículas/química , Hipóxia Celular , Hipóxia/metabolismoRESUMO
Organometallic-mediated chain growth polymerization of readily accessible chemical building blocks is responsible for important commercial and technological advances in polymer science, but the incorporation of heteroatoms into the polymer backbone through these mechanisms remains a challenge. Transition metal π-allyl complexes are well-developed organometallic intermediates for carbon-heteroatom bond formation in small-molecule catalysis yet remain underexplored in polymer science. Here, we developed a regioselective palladium-phosphoramidite-catalyzed chain-growth allylic amination polymerization of vinyl aziridines for the synthesis of novel nitrogen-rich polymers via ambiphilic π-allyl complexes. The polymerization accessed a linear microstructure with four carbons between each nitrogen, which is challenging to achieve through other chain-growth polymerization approaches. The highly regioselective allylic amination polymerization demonstrated the characteristics of a controlled polymerization and was able to achieve molar masses exceeding 20 kg mol-1 with low dispersities (D̵ < 1.3). The identification of the polymer structure and well-defined chain ends were supported by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and chain extension experiments demonstrate opportunities for building more complex materials from this method. A Hammett study was performed to understand the role of the catalyst and monomer structure on regioselectivity, and the data supported a mechanism wherein regioselectivity was primarily controlled by the ligand-metal complex. Postpolymerization desulfonylation provided access to a novel polyamine that demonstrated broad anticancer activity in vitro, which highlights the benefits of unlocking novel polyamine microstructures through regioselective chain-growth allylic amination polymerization.
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Despite their successful implementation in the COVID-19 vaccines, lipid nanoparticles (LNPs) still face a central limitation in the delivery of mRNA payloads: endosomal trapping. Improving upon this inefficiency could afford improved drug delivery systems, paving the way toward safer and more effective mRNA-based medicines. Here, we present polyphenolic nanoparticle platforms (PARCELs) as effective mRNA delivery systems. In brief, our investigation begins with a computationally guided structural analysis of 1825 discrete polyphenolic structural data points across 73 diverse small molecule polyphenols and 25 molecular parameters. We then generate structurally diverse PARCELs, evaluating their in vitro mechanism and activity, ultimately highlighting the superior endosomal escape properties of PARCELs relative to analogous LNPs. Finally, we examine the in vivo biodistribution, protein expression, and therapeutic efficacy of PARCELs in mice. In undertaking this approach, the goal of this study is to establish PARCELs as viable delivery platforms for safe and effective mRNA delivery.
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Nanopartículas , Polifenóis , RNA Mensageiro , Polifenóis/química , Animais , RNA Mensageiro/genética , Camundongos , Nanopartículas/química , Humanos , SARS-CoV-2/efeitos dos fármacos , COVID-19 , Sistemas de Liberação de Medicamentos , Distribuição Tecidual , Lipídeos/química , Endossomos/metabolismo , LipossomosRESUMO
Poly(ethylene glycol) (PEG) is considered to be the "gold standard" among the stealth polymers employed for drug delivery. Using PEG to modify or engineer particles has thus gained increasing interest because of the ability to prolong blood circulation time and reduce nonspecific biodistribution of particles in vivo, owing to the low fouling and stealth properties of PEG. In addition, endowing PEG-based particles with targeting and drug-loading properties is essential to achieve enhanced drug accumulation at target sites in vivo. In this feature article, we focus on recent work on the synthesis of PEG particles, in which PEG is the main component in the particles. We highlight different synthesis methods used to generate PEG particles, the influence of the physiochemical properties of PEG particles on their stealth and targeting properties, and the application of PEG particles in targeted drug delivery.
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Sistemas de Liberação de Medicamentos , Polietilenoglicóis , Polietilenoglicóis/química , Distribuição Tecidual , Polímeros , Engenharia , Portadores de Fármacos/químicaRESUMO
Nature has created various organisms with unique chemical components and multi-scale structures (e.g., foot proteins, toe pads, suckers, setose gill lamellae) to achieve wet adhesion functions to adapt to their complex living environments. These organisms can provide inspirations for designing wet adhesives with mediated drug release behaviors in target locations of biological surfaces. They exhibit conformal and enhanced wet adhesion, addressing the bottleneck of weaker tissue interface adhesion in the presence of body fluids. Herein, it is focused on the research progress of different wet adhesion and bioinspired fabrications, including adhesive protein-based adhesion and inspired adhesives (e.g., mussel adhesion); capillarity and Stefan adhesion and inspired adhesive surfaces (e.g., tree frog adhesion); suction-based adhesion and inspired suckers (e.g., octopus' adhesion); interlocking and friction-based adhesion and potential inspirations (e.g., mayfly larva and teleost adhesion). Other secreted protein-induced wet adhesion is also reviewed and various suckers for other organisms and their inspirations. Notably, one representative application scenario of these bioinspired wet adhesives is highlighted, where they function as efficient drug delivery platforms on target tissues and/or organs with requirements of both controllable wet adhesion and optimized drug release. Finally, the challenges of these bioinspired wet drug delivery platforms in the future is presented.
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Ribonucleic acid (RNA)-based therapies have become an attractive topic in disease intervention, especially with some that have been approved by the FDA such as the mRNA COVID-19 vaccine (Comirnaty, Pfizer-BioNTech, and Spikevax, Moderna) and Patisiran (siRNA-based drug for liver delivery). However, extensive applications are still facing challenges in delivering highly negatively charged RNA to the targeted site. Therapeutic delivery strategies including RNA modifications, RNA conjugates, and RNA polyplexes and delivery platforms such as viral vectors, nanoparticle-based delivery platforms, and hydrogel-based delivery platforms as potential nucleic acid-releasing depots have been developed to enhance their cellular uptake and protect nucleic acid from being degraded by immune systems. Here, we review the growing number of viral vectors, nanoparticles, and hydrogel-based RNA delivery systems; describe RNA loading/release mechanism induced by environmental stimulations including light, heat, pH, or enzyme; discuss their physical or chemical interactions; and summarize the RNA therapeutics release period (temporal) and their target cells/organs (spatial). Finally, we describe current concerns, highlight current challenges and future perspectives of RNA-based delivery systems, and provide some possible research areas that provide opportunities for clinical translation of RNA delivery carriers.
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Nanopartículas , Ácidos Nucleicos , Humanos , RNA , Vacinas contra COVID-19 , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Sistemas de Liberação de Medicamentos , HidrogéisRESUMO
A central goal of chemical and drug delivery sciences is to maximize the therapeutic efficacy of a given drug at the lowest possible dose. Here, we report a generalizable strategy that can be utilized to improve the delivery of mRNA drugs using lipid nanoparticles (LNPs), the clinically approved chemistry platforms utilized in the Moderna and Pfizer/BioNTech COVID-19 vaccines. In brief, our strategy updates the chemistry of LNPs to incorporate adenosine triphosphate (ATP) alongside mRNA, a modification that results in upward of a 79-fold increase in LNP-delivered mRNA-encoded protein expression in vitro and a 24-fold increase in vivo when compared to parent mRNA LNP formulations that do not contain ATP. Notably, we find that our ATP co-delivery strategy increases LNP-delivered mRNA-encoded protein expression across eight different LNP chemistries and three different cell lines, under normoxia and hypoxia, and in a well-tolerated fashion. Notably, our strategy also improves the expression of mRNA encoding for intracellular and secreted proteins both in vitro and in vivo, highlighting the utility of leveraging ATP co-delivery within mRNA LNPs as a means to increase protein expression. In developing this strategy, we hope that we have provided a simple yet powerful approach to improving mRNA LNPs that may one day be useful in developing therapies for human disease.
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Trifosfato de Adenosina , COVID-19 , Humanos , Vacinas contra COVID-19 , RNA Mensageiro/genéticaRESUMO
The semi-permeable round window membrane (RWM) is the gateway to the cochlea. Although the RWM is considered a minimally invasive and clinically accepted route for localised drug delivery to the cochlea, overcoming this barrier is challenging, hindering development of effective therapies for hearing loss. Neurotrophin 3 (NT3) is an emerging treatment option for hearing loss, but its therapeutic effect relies on sustained delivery across the RWM into the cochlea. Silica supraparticles (SPs) are drug delivery carriers capable of providing long-term NT3 delivery, when injected directly into the guinea pig cochlea. However, for clinical translation, a RWM delivery approach is desirable. Here, we aimed to test approaches to improve the longevity and biodistribution of NT3 inside the cochlea after RWM implantation of SPs in guinea pigs and cats. Three approaches were tested (i) coating the SPs to slow drug release (ii) improving the retention of SPs on the RWM using a clinically approved gel formulation and (iii) permeabilising the RWM with hyaluronic acid. A radioactive tracer (iodine 125: 125I) tagged to NT3 (125I NT3) was loaded into the SPs to characterise drug pharmacokinetics in vitro and in vivo. The neurotrophin-loaded SPs were coated using a chitosan and alginate layer-by-layer coating strategy, named as '(Chi/Alg)SPs', to promote long term drug release. The guinea pigs were implanted with 5× 125I NT3 loaded (Chi/Alg) SPs on the RWM, while cats were implanted with 30× (Chi/Alg) SPs. A cohort of animals were also implanted with SPs (controls). We found that the NT3 loaded (Chi/Alg)SPs exhibited a more linear release profile compared to NT3 loaded SPs alone. The 125I NT3 loaded (Chi/Alg)SPs in fibrin sealant had efficient drug loading (~5 µg of NT3 loaded per SP that weights ~50 µg) and elution capacities (~49% over one month) in vitro. Compared to the SPs in fibrin sealant, the (Chi/Alg)SPs in fibrin sealant had a significantly slower 125I NT3 drug release profile over the first 7 days in vitro (~12% for (Chi/Alg) SPs in fibrin sealant vs ~43% for SPs in fibrin sealant). One-month post-implantation of (Chi/Alg) SPs, gamma count measurements revealed an average of 0.3 µg NT3 remained in the guinea pig cochlea, while for the cat, 1.3 µg remained. Histological analysis of cochlear tissue revealed presence of a 125I NT3 signal localised in the basilar membrane of the lower basal turn in some cochleae after 4 weeks in guinea pigs and 8 weeks in cats. Comparatively, and in contrast to the in vitro release data, implantation of the SPs presented better NT3 retention and distribution inside the cochlea in both the guinea pigs and cats. No significant difference in drug entry was observed upon acute treatment of the RWM with hyaluronic acid. Collectively, our findings indicate that SPs and (Chi/Alg)SPs can facilitate drug transfer across the RWM, with detectable levels inside the cat cochlea even after 8 weeks with the intracochlear approach. This is the first study to examine neurotrophin pharmacokinetics in the cochlea for such an extended period of times in these two animal species. Whilst promising, we note that outcomes between animals were variable, and opposing results were found between in vitro and in vivo release studies. These findings have important clinical ramifications, emphasising the need to understand the physical properties and mechanics of this complex barrier in parallel with the development of therapies for hearing loss.
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Surdez , Perda Auditiva , Animais , Cobaias , Gatos , Adesivo Tecidual de Fibrina/farmacologia , Ácido Hialurônico , Distribuição Tecidual , Cóclea , Janela da Cóclea/patologia , Janela da Cóclea/cirurgia , Perda Auditiva/terapia , Fatores de Crescimento NeuralRESUMO
The concept of using mRNA to produce its own medicine in situ in the body makes it an ideal drug candidate, holding great potential to revolutionize the way we approach medicine. The unique characteristics of mRNA, as well as its customizable biomedical functions, call for the rational design of delivery systems to protect and transport mRNA molecules. In this review, a nanoparticle toolkit is presented for the development of mRNA-based therapeutics from a drug delivery perspective. Nano-delivery systems derived from either natural systems or chemical synthesis, in the nature of organic or inorganic materials, are summarised. Delivery strategies in controlling the tissue targeting and mRNA release, as well as the role of nanoparticles in building and boosting the activity of mRNA drugs, have also been introduced. In the end, our insights into the clinical and translational development of mRNA nano-drugs are presented.
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Nanopartículas , Humanos , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Sistemas de Liberação de Fármacos por NanopartículasRESUMO
Short interfering RNAs (siRNA) are a powerful class of genetic medicines whose clinical translation can be hindered by their suboptimal delivery properties in vivo. Here, we provide a clinically focused overview that summarizes ongoing siRNA clinical trials from the perspective of innovations in nonviral delivery strategies. More specifically, our review begins by highlighting the delivery barriers and physiochemical properties of siRNA that make it challenging to deliver it in vivo. We then provide commentary on specific delivery strategies, including sequence modification, siRNA ligand conjugation, and nanoparticle and exosomal packaging, each of which can be used to control the delivery of siRNA therapies in living systems. Last, we provide a summary table of ongoing siRNA clinical trials which also highlights the indication of use, target, and National Clinical Trial (NCT) number associated with each entry. In writing this review, our work aims to highlight the key challenges and strategies for effective nonviral siRNA delivery in vivo, while simultaneously summarizing information on ongoing clinical trials for siRNA therapy in humans.
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Nanopartículas , Humanos , RNA Interferente Pequeno , Nanopartículas/químicaRESUMO
Hypoxia is a common hallmark of human disease that is characterized by abnormally low oxygen levels in the body. While the effects of hypoxia on many small molecule-based drugs are known, its effects on several classes of next-generation medications including messenger RNA therapies warrant further study. Here, we provide an efficacy- and mechanism-driven study that details how hypoxia impacts the cellular response to mRNA therapies delivered using 4 different chemistries of lipid nanoparticles (LNPs, the frontrunner class of drug delivery vehicles for translational mRNA therapy utilized in the Moderna and Pfizer/BioNTech COVID-19 vaccines). Specifically, our work provides a comparative analysis as to how various states of oxygenation impact LNP-delivered mRNA expression, cellular association, endosomal escape, and intracellular ATP concentrations following treatment with 4 different LNPs across 3 different cell lines. In brief, we first identify that hypoxic cells express less LNP-delivered mRNA into protein than normoxic cells. Next, we identify generalizable cellular reoxygenation protocols that can reverse the negative effects that hypoxia imparts on LNP-delivered mRNA expression. Finally, mechanistic studies that utilize fluorescence-activated cell sorting, confocal microscopy, and enzyme inhibition reveal that decreases in mRNA expression correlate with decreases in intracellular ATP (rather than with differences in mRNA LNP uptake pathways). In presenting this data, we hope that our work provides a comprehensive efficacy and mechanism-driven study that explores the impact of differential oxygenation on LNP-delivered mRNA expression while simultaneously establishing fundamental criteria that may one day be useful for the development of mRNA drugs to treat hypoxia-associated disease.
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COVID-19 , Nanopartículas , Humanos , Lipídeos , RNA Mensageiro/genética , Vacinas contra COVID-19 , Lipossomos , Hipóxia , Trifosfato de Adenosina , RNA Interferente Pequeno/genéticaRESUMO
SARS-CoV-2, the etiologic agent of the COVID-19 pandemic, is a highly contagious positive-sense RNA virus. Its explosive community spread and the emergence of new mutant strains have created palpable anxiety even in vaccinated people. The lack of effective anticoronavirus therapeutics continues to be a major global health concern, especially due to the high evolution rate of SARS-CoV-2. The nucleocapsid protein (N protein) of SARS-CoV-2 is highly conserved and involved in diverse processes of the virus replication cycle. Despite its critical role in coronavirus replication, N protein remains an unexplored target for anticoronavirus drug discovery. Here, we demonstrate that a novel compound, K31, binds to the N protein of SARS-CoV-2 and noncompetitively inhibits its binding to the 5' terminus of the viral genomic RNA. K31 is well tolerated by SARS-CoV-2-permissive Caco2 cells. Our results show that K31 inhibited SARS-CoV-2 replication in Caco2 cells with a selective index of ~58. These observations suggest that SARS-CoV-2 N protein is a druggable target for anticoronavirus drug discovery. K31 holds promise for further development as an anticoronavirus therapeutic. IMPORTANCE The lack of potent antiviral drugs for SARS-CoV-2 is a serious global health concern, especially with the explosive spread of the COVID-19 pandemic worldwide and the constant emergence of new mutant strains with improved human-to-human transmission. Although an effective coronavirus vaccine appears promising, the lengthy vaccine development processes in general and the emergence of new mutant viral strains with a potential to evade the vaccine always remain a serious concern. The antiviral drugs targeted to the highly conserved targets of viral or host origin remain the most viable and timely approach, easily accessible to the general population, in combating any new viral illness. The majority of anticoronavirus drug development efforts have focused on spike protein, envelope protein, 3CLpro, and Mpro. Our results show that virus-encoded N protein is a novel therapeutic target for anticoronavirus drug discovery. Due to its high conservation, the anti-N protein inhibitors will likely have broad-spectrum anticoronavirus activity.
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COVID-19 , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Pandemias/prevenção & controle , Células CACO-2 , Descoberta de Drogas , Antivirais/uso terapêutico , Proteínas do NucleocapsídeoRESUMO
Feline infectious peritonitis (FIP) is a serious viral illness in cats, caused by feline coronavirus. Once a cat develops clinical FIP, the prognosis is poor. The effective treatment strategy for coronavirus infections with immunopathological complications such as SARS-CoV-2, MERS, and FIP is focused on antiviral and immunomodulatory agents to inhibit virus replication and enhance the protective immune response. In this article we report the binding and conformational alteration of feline alphacoronavirus (FCoV) nucleocapsid protein by a novel compound K31. K31 noncompetitively inhibited the interaction between the purified nucleocapsid protein and the synthetic 5' terminus of viral genomic RNA in vitro. K31 was well tolerated by cells and inhibited FCoV replication in cell culture with a selective index of 115. A single dose of K31inhibited FCoV replication to an undetectable level in 24 h post treatment. K31 did not affect the virus entry to the host cell but inhibited the postentry steps of virus replication. The nucleocapsid protein forms ribonucleocapsid in association with the viral genomic RNA that serves as a template for transcription and replication of the viral genome. Our results show that K31 treatment disrupted the structural integrity of ribonucleocapsid in virus-infected cells. After the COVID-19 pandemic, most of the antiviral drug development strategies have focused on RdRp and proteases encoded by the viral genome. Our results have shown that nucleocapsid protein is a druggable target for anticoronavirus drug discovery.
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Antivirais , Coronavirus Felino , Peritonite Infecciosa Felina , Proteínas do Nucleocapsídeo , Replicação Viral , Animais , Gatos , Antivirais/farmacologia , Antivirais/uso terapêutico , Técnicas de Cultura de Células , Coronavirus Felino/efeitos dos fármacos , Coronavirus Felino/fisiologia , Peritonite Infecciosa Felina/tratamento farmacológico , RNA Viral/genética , Replicação Viral/efeitos dos fármacosRESUMO
Innovative food packaging techniques provide extrinsic systems for ensuring the quality and safety of food products. Recent research has focused on the development of multifunctional nanocomposites towards emerging active and sustainable food packaging (ASFP) systems. Specifically, diverse biomass-derived nanocomposite films (BNFs) are engineered via incorporating functional nanomaterials into the naturally-occurring biopolymers (e.g., polysaccharides and proteins). Such BNFs lead to minimum environmental risks compared to petroleum-derived materials, while exhibit improved physicochemical properties and functionalities, demonstrating great potential for ASFP. This review provides a summary of state-of-art BNFs based on their composition and application. We also highlight the advantages of BNFs for agricultural products. Particularly, the interactions between the biomass matrix and the nanomaterials are discussed to provide insightful rationales for designing high-performance BNFs. We envision that BNFs will not only be emerged as the dominant food packaging materials, but also contribute to the international trade and addressing the global food crisis.
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Embalagem de Alimentos , Nanocompostos , Biomassa , Comércio , InternacionalidadeRESUMO
Ionic polymers have been proven to be promising adsorbents in recovering Au(III) due to their advantages of simple synthesis and high adsorption efficiency. However, the unclarity of the relationship between the adsorption ability of ionic polymers and their cationic structures hinders further optimization of their adsorption performance. This study synthesized a series of ionic polymers with pyridinium, imidazolium, piperidinium, pyrrolidinium, and triethylammonium cations to discover the effects of the cationic structure on their adsorption properties. Experimental results show that the existence of anion-π interaction between aromatic cations and [AuCl4]- makes the aromatic cations-anion interaction stronger, which does not enhance the adsorption performance of the aromatic-based ionic polymer. This is due to the charge delocalization in the aromatic ring, resulting in a lower electrostatic potential (ESP) of aromatic cations than that of aliphatic cations with a localized charge. The higher the ESP of cations, the better the adsorption performance of the corresponding ionic polymer. This study serves as a deep understanding of the cationic structure-adsorptive performance relationship of the ionic polymer at the molecular level and further provides a theoretical guidance to optimize the adsorption performance of ionic polymers.
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Hearing loss is the most prevalent sensory disorder affecting nearly half a billion people worldwide. Aside from devices to assist hearing, such as hearing aids and cochlear implants, a drug treatment for hearing loss has yet to be developed. The neurotrophin family of growth factors has long been established as a potential therapy, however delivery of these factors into the inner ear at therapeutic levels over a sustained period of time has remained a challenge restricting clinical translation. We previously demonstrated that direct delivery of exogenous neurotrophin-3 (NT3) in the guinea pig cochleae via a bolus injection was rapidly cleared from the inner ear, with almost complete elimination 3 days post-treatment. Here, we explored the potential of suprapaticles (SPs) for NT3 delivery to the inner ear to achieve sustained delivery over time. SPs are porous spheroid structures comprised of smaller colloidal silica nanoparticles that provide a platform for long-term controlled release of therapeutics. This study aimed to assess the pharmacokinetics and biodistribution of SP-delivered NT3. We used a radioactive tracer (iodine 125: 125I) to label the NT3 to determine the loading, retention and distribution of NT3 delivered via SPs. Gamma measurements taken from 125I NT3 loaded SPs revealed high drug loading (an average of 5.3 µg of NT3 loaded per SP weighing 50 µg) and elution capacities in vitro (67% cumulative release over one month). Whole cochlear gamma measurements from SP-implanted cochleae harvested at various time points revealed detection of 125I NT3 in the guinea pig cochlea after one month, with 3.6 and 10% of the loaded drug remaining in the intracochlear and round window-implanted cochleae respectively. Autoradiography analysis of cochlear micro-sections revealed widespread 125I NT3 distribution after intracochlear SP delivery, but more restricted distribution with the round window delivery approach. Collectively, drug delivery into the inner ear using SPs support sustained, long-term availability and release of neurotrophins in the inner ear.
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Surdez , Orelha Interna , Animais , Cóclea , Surdez/tratamento farmacológico , Cobaias , Humanos , Neurotrofina 3 , Distribuição TecidualRESUMO
Hearing loss is the most common sensory deficit worldwide with no approved therapeutics for treatment. Local neurotrophin delivery into the cochlea has shown great potential in protecting and repairing the sensory cells important for hearing. However, delivery of these factors into the inner ear at therapeutic levels over a sustained period of time has remained a challenge restricting clinical translation. We have developed a method to test the pharmacokinetics of neurotrophin released from porous silica particles called 'supraparticles' that can provide sustained release of neurotrophins to the inner ear.â¢This report describes a radiolabeling method to examine neurotrophin retention and distribution in the cochlea. The neurotrophin was labeled with a radioactive tracer (iodine 125: 125I) and delivered into the cochlea via the supraparticle system.â¢Gamma counts reveal drug levels and clearance in the intact cochlea, as well as accumulation in off-target organs (safety test). Autoradiography analyses using film and emulsion permit quantification and visualization of drug distribution at the cellular level. The method has a detection limit of 0.8 pg of radiolabeled neurotrophin-3 in cochlear sections exposed to film.â¢The tracer 125I with a half-life of 59.4 days can be used to label other drugs/substances with a tyrosine residue and therefore be broadly applicable for long-term pharmacokinetic studies in other systems.