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1.
IET Nanobiotechnol ; 16(3): 85-91, 2022 May.
Article in English | MEDLINE | ID: covidwho-1758388

ABSTRACT

Mesoporous magnetic nanoparticles of haematite were synthesised using plant extracts according to bioethics principles. The structural, physical and chemical properties of mesoporous Fe2 O3 nanoparticles synthesised with the green chemistry approach were evaluated by XRD, SEM, EDAX, BET, VSM and HRTEM analysis. Then, their toxicity against normal HUVECs and MCF7 cancer cells was evaluated by MTT assay for 48 h. These biogenic mesoporous magnetic nanoparticles have over 71% of doxorubicin loading efficiency, resulting in a 50% reduction of cancer cells at a 0.5 µg.ml-1 concentration. Therefore, it is suggested that mesoporous magnetic nanoparticles be used as a multifunctional agent in medicine (therapeutic-diagnostic). The produced mesoporous magnetic nanoparticles with its inherent structural properties such as polygonal structure (increasing surface area to particle volume) and porosity with large pore volume became a suitable substrate for loading the anti-cancer drug doxorubicin.


Subject(s)
Nanoparticles , Silicon Dioxide , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation , Humans , Nanoparticles/chemistry , Porosity , Silicon Dioxide/chemistry
2.
Int J Mol Sci ; 23(4)2022 Feb 21.
Article in English | MEDLINE | ID: covidwho-1705083

ABSTRACT

We theoretically investigated the adsorption of two common anti-COVID drugs, favipiravir and chloroquine, on fluorinated C60 fullerene, decorated with metal ions Cr3+, Fe2+, Fe3+, Ni2+. We focused on the effect of fluoridation on the interaction of fullerene with metal ions and drugs in an aqueous solution. We considered three model systems, C60, C60F2 and C60F48, and represented pristine, low-fluorinated and high-fluorinated fullerenes, respectively. Adsorption energies, deformation of fullerene and drug molecules, frontier molecular orbitals and vibrational spectra were investigated in detail. We found that different drugs and different ions interacted differently with fluorinated fullerenes. Cr3+ and Fe2+ ions lead to the defluorination of low-fluorinated fullerenes. Favipiravir also leads to their defluorination with the formation of HF molecules. Therefore, fluorinated fullerenes are not suitable for the delivery of favipiravir and similar drugs molecules. In contrast, we found that fluorine enhances the adsorption of Ni2+ and Fe3+ ions on fullerene and their activity to chloroquine. Ni2+-decorated fluorinated fullerenes were found to be stable and suitable carriers for the loading of chloroquine. Clear shifts of infrared, ultraviolet and visible spectra can provide control over the loading of chloroquine on Ni2+-doped fluorinated fullerenes.


Subject(s)
Amides/chemistry , Antiviral Agents/chemistry , Chloroquine/chemistry , Fullerenes/chemistry , Metals/chemistry , Pyrazines/chemistry , COVID-19 , Density Functional Theory , Drug Carriers/chemistry , Drug Delivery Systems , Halogenation , Models, Molecular , Nickel/chemistry
3.
Int J Mol Sci ; 23(3)2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1625612

ABSTRACT

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl- currents and intracellular Ca2+ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca2+ activated Cl- channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca2+ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.


Subject(s)
Niclosamide/administration & dosage , Pneumonia/drug therapy , Respiratory System/drug effects , Animals , Asthma/drug therapy , Asthma/metabolism , Asthma/pathology , COVID-19/complications , COVID-19/drug therapy , Cells, Cultured , Disease Models, Animal , Drug Carriers/chemistry , Drug Compounding , Humans , Hydrogels/chemistry , Instillation, Drug , Mice , Microspheres , Mucus/drug effects , Mucus/metabolism , Nanospheres/administration & dosage , Nanospheres/chemistry , Niclosamide/chemistry , Niclosamide/pharmacokinetics , Pneumonia/pathology , Polyethylene Glycols/chemistry , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory System/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Trachea
4.
ACS Appl Bio Mater ; 4(12): 8110-8128, 2021 12 20.
Article in English | MEDLINE | ID: covidwho-1597218

ABSTRACT

The design of advanced nanobiomaterials to improve analytical accuracy and therapeutic efficacy has become an important prerequisite for the development of innovative nanomedicines. Recently, phospholipid nanobiomaterials including 2-methacryloyloxyethyl phosphorylcholine (MPC) have attracted great attention with remarkable characteristics such as resistance to nonspecific protein adsorption and cell adhesion for various biomedical applications. Despite many recent reports, there is a lack of comprehensive review on the phospholipid nanobiomaterials from synthesis to diagnostic and therapeutic applications. Here, we review the synthesis and characterization of phospholipid nanobiomaterials focusing on MPC polymers and highlight their attractive potentials for applications in micro/nanofabricated fluidic devices, biosensors, lab-on-a-chip, drug delivery systems (DDSs), COVID-19 potential usages for early diagnosis and even treatment, and artificial extracellular matrix scaffolds for cellular engineering.


Subject(s)
Biocompatible Materials/chemistry , Drug Carriers/chemistry , Lab-On-A-Chip Devices , Nanostructures/chemistry , Phospholipids/chemistry , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Humans , Microscopy, Confocal , SARS-CoV-2/isolation & purification
5.
Molecules ; 27(1)2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1580565

ABSTRACT

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (-36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer-Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.


Subject(s)
Azetidines/pharmacokinetics , Drug Carriers/chemistry , Drug Liberation , Liposomes/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Purines/pharmacokinetics , Pyrazoles/pharmacokinetics , Sulfonamides/pharmacokinetics , Administration, Oral , Animals , Azetidines/administration & dosage , Azetidines/chemistry , Biological Availability , Male , Purines/administration & dosage , Purines/chemistry , Pyrazoles/administration & dosage , Pyrazoles/chemistry , Rats , Rats, Wistar , Sulfonamides/administration & dosage , Sulfonamides/chemistry
6.
Chem Pharm Bull (Tokyo) ; 69(12): 1141-1159, 2021.
Article in English | MEDLINE | ID: covidwho-1546823

ABSTRACT

Considerable efforts have been made on the development of lipid nanoparticles (LNPs) for delivering of nucleic acids in LNP-based medicines, including a first-ever short interfering RNA (siRNA) medicine, Onpattro, and the mRNA vaccines against the coronavirus disease 2019 (COVID-19), which have been approved and are currently in use worldwide. The successful rational design of ionizable cationic lipids was a major breakthrough that dramatically increased delivery efficiency in this field. The LNPs would be expected to be useful as a platform technology for the delivery of various therapeutic modalities for genome editing and even for undiscovered therapeutic mechanisms. In this review, the current progress of my research, including the molecular design of pH-sensitive cationic lipids, their applications for various tissues and cell types, and for delivering various macromolecules, including siRNA, antisense oligonucleotide, mRNA, and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system will be described. Mechanistic studies regarding relationships between the physicochemical properties of LNPs, drug delivery, and biosafety are also summarized. Furthermore, current issues that need to be addressed for next generation drug delivery systems are discussed.


Subject(s)
Drug Carriers/chemistry , Lipids/chemistry , Liposomes/chemistry , Nanoparticles/chemistry , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Cations/chemistry , Hydrogen-Ion Concentration , RNA, Guide/chemistry , RNA, Guide/metabolism , RNA, Small Interfering/chemistry , RNA, Small Interfering/metabolism , SARS-CoV-2/isolation & purification , /metabolism
7.
Acc Chem Res ; 54(23): 4283-4293, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1521679

ABSTRACT

After decades of extensive fundamental studies and clinical trials, lipid nanoparticles (LNPs) have demonstrated effective mRNA delivery such as the Moderna and Pfizer-BioNTech vaccines fighting against COVID-19. Moreover, researchers and clinicians have been investigating mRNA therapeutics for a variety of therapeutic indications including protein replacement therapy, genome editing, and cancer immunotherapy. To realize these therapeutics in the clinic, there are many formidable challenges. First, novel delivery systems such as LNPs with high delivery efficiency and low toxicity need to be developed for different cell types. Second, mRNA molecules need to be engineered for improved pharmaceutical properties. Lastly, the LNP-mRNA nanoparticle formulations need to match their therapeutic applications.In this Account, we summarize our recent advances in the design and development of various classes of lipids and lipid derivatives, which can be formulated with multiple types of mRNA molecules to treat diverse diseases. For example, we conceived a series of ionizable lipid-like molecules based on the structures of a benzene core, an amide linker, and hydrophobic tails. We identified N1,N3,N5-tris(3-(didodecylamino)propyl)benzene-1,3,5-tricarboxamide (TT3) as a lead compound for mRNA delivery both in vitro and in vivo. Moreover, we tuned the biodegradability of these lipid-like molecules by introducing branched ester or linear ester chains. Meanwhile, inspired by biomimetic compounds, we synthesized vitamin-derived lipids, chemotherapeutic conjugated lipids, phospholipids, and glycolipids. These scaffolds greatly broaden the chemical space of ionizable lipids for mRNA delivery. In another section, we highlight our efforts on the research direction of mRNA engineering. We previously optimized mRNA chemistry using chemically-modified nucleotides to increase the protein expression, such as pseudouridine (ψ), 5-methoxyuridine (5moU), and N1-methylpseudouridine (me1ψ). Also, we engineered the sequences of mRNA 5' untranslated regions (5'-UTRs) and 3' untranslated regions (3'-UTRs), which dramatically enhanced protein expression. With the progress of LNP development and mRNA engineering, we consolidate these technologies and apply them to treat diseases such as genetic disorders, infectious diseases, and cancers. For instance, TT3 and its analog-derived lipid-like nanoparticles can effectively deliver factor IX or VIII mRNA and recover the clotting activity in hemophilia mouse models. Engineered mRNAs encoding SARS-CoV-2 antigens serve well as vaccine candidates against COVID-19. Vitamin-derived lipid nanoparticles loaded with antimicrobial peptide-cathepsin B mRNA enable adoptive macrophage transfer to treat multidrug resistant bacterial sepsis. Biomimetic lipids such as phospholipids formulated with mRNAs encoding costimulatory receptors lead to enhanced cancer immunotherapy.Overall, lipid-mRNA nanoparticle formulations have considerably benefited public health in the COVID-19 pandemic. To expand their applications in clinical use, research work from many disciplines such as chemistry, engineering, materials, pharmaceutical sciences, and medicine need to be integrated. With these collaborative efforts, we believe that more and more lipid-mRNA nanoparticle formulations will enter the clinic in the near future and benefit human health.


Subject(s)
Drug Carriers/chemistry , Liposomes/chemistry , Nanoparticles/chemistry , RNA, Messenger/chemistry , Animals , Benzamides/chemistry , Biomimetic Materials/chemistry , Communicable Diseases/immunology , Communicable Diseases/therapy , Disease Models, Animal , Genetic Diseases, Inborn/immunology , Genetic Diseases, Inborn/therapy , Humans , Mice , Neoplasms/immunology , Neoplasms/therapy , Phospholipids/chemistry , RNA, Messenger/metabolism , RNA, Messenger/therapeutic use , Untranslated Regions , Vitamins/chemistry
8.
Chem Biol Interact ; 351: 109706, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1464614

ABSTRACT

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.


Subject(s)
Drug Carriers/chemistry , Lung/metabolism , Peptides/administration & dosage , Proteins/administration & dosage , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Lung/drug effects , Lung Diseases/drug therapy , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Peptides/therapeutic use , Proteins/therapeutic use
9.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1186: 123015, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1487818

ABSTRACT

The potential of lipid nanoparticles (LNPs) as nucleic acid delivery vehicles has been demonstrated in recent years, culminating in the emergency use approval of LNP-based mRNA SARS-CoV-2 vaccines in late 2020. The determination of RNA content relative to LNP size can be important to the understanding of efficacy and adverse effects. This work presents the first description of a facile and rapid analytical method for online, size-dependent RNA payload distribution measurement using data from multi-angle light scattering, ultraviolet and refractive index detectors following separation of the LNPs by size-exclusion chromatography. The analysis was validated by size-based fractionation of the LNPs with subsequent offline analysis of the fractions. Four LNPs formulated with different PEG-lipids and different lipid compositions were tested. Good agreement was observed between the online and offline size-based RNA distributions among all four LNPs, demonstrating the utility of the online method for LNP-encapsulated RNA in general, and suggesting a means for simplified biophysical quantitation of a dosing-related critical quality attribute.


Subject(s)
COVID-19 Vaccines/chemistry , Chromatography, Gel/methods , Drug Carriers/chemistry , Nanoparticles/chemistry , RNA, Messenger/chemistry , RNA, Viral/chemistry , SARS-CoV-2/genetics , COVID-19/virology , COVID-19 Vaccines/immunology , Drug Delivery Systems , Humans , Lipids/chemistry , Particle Size , RNA, Messenger/immunology , RNA, Viral/immunology , SARS-CoV-2/chemistry , SARS-CoV-2/immunology
10.
Curr Top Med Chem ; 20(11): 915-962, 2020.
Article in English | MEDLINE | ID: covidwho-1453165

ABSTRACT

BACKGROUND: Emerging viral zoonotic diseases are one of the major obstacles to secure the "One Health" concept under the current scenario. Current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. Moreover, most of the viral zoonoses originate from the wildlife and poor knowledge about the global virome database renders it difficult to predict future outbreaks. Thus, alternative management strategy in terms of improved prophylactic vaccines and their delivery systems; rapid and efficient diagnostics and effective targeted therapeutics are the need of the hour. METHODS: Structured literature search has been performed with specific keywords in bibliographic databases for the accumulation of information regarding current nanomedicine interventions along with standard books for basic virology inputs. RESULTS: Multi-arrayed applications of nanomedicine have proved to be an effective alternative in all the aspects regarding the prevention, diagnosis, and control of zoonotic viral diseases. The current review is focused to outline the applications of nanomaterials as anti-viral vaccines or vaccine/drug delivery systems, diagnostics and directly acting therapeutic agents in combating the important zoonotic viral diseases in the recent scenario along with their potential benefits, challenges and prospects to design successful control strategies. CONCLUSION: This review provides significant introspection towards the multi-arrayed applications of nanomedicine to combat several important zoonotic viral diseases.


Subject(s)
Drug Delivery Systems/methods , Viral Vaccines/chemistry , Viral Zoonoses/diagnosis , Viral Zoonoses/prevention & control , Viral Zoonoses/therapy , Viruses/drug effects , Animals , Animals, Wild , Biosensing Techniques , Drug Carriers/chemistry , Drug Compounding , Drug Liberation , Humans , Nanomedicine , Nanoparticles/chemistry , Polymers/chemistry , Polymers/metabolism , Transfection , Viruses/metabolism
11.
Carbohydr Polym ; 273: 118605, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1370153

ABSTRACT

Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biomimetic Materials/chemistry , Chitosan/analogs & derivatives , Drug Carriers/chemistry , Endopeptidases/pharmacology , Nanoparticles/chemistry , A549 Cells , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Biomimetic Materials/metabolism , Chitosan/chemistry , Chitosan/metabolism , Drug Carriers/metabolism , Drug Liberation , Endopeptidases/chemistry , Humans , Nanoparticles/metabolism , Streptococcus pneumoniae/drug effects
13.
J Mater Chem B ; 9(38): 7878-7908, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1373457

ABSTRACT

Infectious diseases caused by bacteria, viruses, and fungi and their global spread pose a great threat to human health. The 2019 World Health Organization report predicted that infection-related mortality will be similar to cancer mortality by 2050. Particularly, the global cumulative numbers of the recent outbreak of coronavirus disease (COVID-19) have reached 110.7 million cases and over 2.4 million deaths as of February 23, 2021. Moreover, the crisis of these infectious diseases exposes the many problems of traditional diagnosis, treatment, and prevention, such as time-consuming and unselective detection methods, the emergence of drug-resistant bacteria, serious side effects, and poor drug delivery. There is an urgent need for rapid and sensitive diagnosis as well as high efficacy and low toxicity treatments. The emergence of nanomedicine has provided a promising strategy to greatly enhance detection methods and drug treatment efficacy. Owing to their unique optical, magnetic, and electrical properties, nanoparticles (NPs) have great potential for the fast and selective detection of bacteria, viruses, and fungi. NPs exhibit remarkable antibacterial activity by releasing reactive oxygen species and metal ions, exerting photothermal effects, and causing destruction of the cell membrane. Nano-based delivery systems can further improve drug permeability, reduce the side effects of drugs, and prolong systemic circulation time and drug half-life. Moreover, effective drugs against COVID-19 are still lacking. Recently, nanomedicine has shown great potential to accelerate the development of safe and novel anti-COVID-19 drugs. This article reviews the fundamental mechanisms and the latest developments in the treatment and diagnosis of bacteria, viruses, and fungi and discusses the challenges and perspectives in the application of nanomedicine.


Subject(s)
Anti-Infective Agents/therapeutic use , Communicable Diseases/drug therapy , Nanomedicine , Anti-Infective Agents/chemistry , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Communicable Diseases/diagnosis , Communicable Diseases/microbiology , Communicable Diseases/virology , Drug Carriers/chemistry , Humans , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification
14.
J Mater Chem B ; 9(36): 7328-7346, 2021 09 22.
Article in English | MEDLINE | ID: covidwho-1351983

ABSTRACT

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) caused the COVID-19 pandemic. According to the World Health Organization, this pandemic continues to be a serious threat to public health due to the worldwide spread of variants and their higher rate of transmissibility. A range of measures are necessary to slow the pandemic and save lives, which include constant evaluation and the careful adjustment of public-health responses augmented by medical treatments, vaccines and protective gear. It is hypothesized that nanostructured particulates underpinned by nanoscience and quantum science yield high-performing antiviral strategies, which can be applied in preventive, diagnostic, and therapeutic applications such as face masks, respirators, COVID test kits, vaccines, and drugs. This review is aimed at providing comprehensive and cohesive perspectives on various nanostructures that are suited to intensifying and amplifying the effectiveness of antiviral strategies. Growing scientific literature over the past eighteen months indicates that quantum dots, iron oxide, silicon oxide, polymeric and metallic nanoparticles have been employed in COVID-19 diagnostic assays, vaccines, and personal protective equipment (PPE). Quantum dots have displayed their suitability as more sensitive imaging probes in diagnostics and prognostics, and as controlled drug-release carriers that target the virus. Nanoscience and quantum science have assisted the design of advanced vaccine delivery since nanostructured materials are suited for antigen delivery, as mimics of viral structures and as adjuvants. Furthermore, the quantum science- and nanoscience-supported tailored functionalization of nanostructured materials offers insight and pathways to deal with future pandemics. This review seeks to illustrate several examples, and to explain the underpinning quantum science and nanoscience phenomena, which include wave functions, electrostatic interactions, van der Waals forces, thermal and electrodynamic fluctuations, dispersion forces, local field-enhancement effects, and the generation of reactive oxygen species (ROS). This review discusses how nanostructured materials are helpful in the detection, prevention, and treatment of the SARS-CoV-2 infection, other known viral infection diseases, and future pandemics.


Subject(s)
Antiviral Agents/chemistry , Nanostructures/chemistry , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Disinfection/methods , Drug Carriers/chemistry , Humans , Personal Protective Equipment , Reactive Oxygen Species/chemistry , Reactive Oxygen Species/metabolism , SARS-CoV-2/isolation & purification , Virus Diseases/drug therapy , Virus Diseases/virology
15.
ACS Appl Bio Mater ; 4(8): 5839-5870, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1345532

ABSTRACT

Precisely engineered magnetic nanoparticles (MNPs) have been widely explored for applications including theragnostic platforms, drug delivery systems, biomaterial/device coatings, tissue engineering scaffolds, performance-enhanced therapeutic alternatives, and even in SARS-CoV-2 detection strips. Such popularity is due to their unique, challenging, and tailorable physicochemical/magnetic properties. Given the wide biomedical-related potential applications of MNPs, significant achievements have been reached and published (exponentially) in the last five years, both in synthesis and application tailoring. Within this review, and in addition to essential works in this field, we have focused on the latest representative reports regarding the biomedical use of MNPs including characteristics related to their oriented synthesis, tailored geometry, and designed multibiofunctionality. Further, actual trends, needs, and limitations of magnetic-based nanostructures for biomedical applications will also be discussed.


Subject(s)
Magnetics , Magnetite Nanoparticles/chemistry , Animals , COVID-19/diagnosis , COVID-19/virology , Drug Carriers/chemistry , History, 17th Century , Humans , Magnetite Nanoparticles/history , SARS-CoV-2/isolation & purification , Theranostic Nanomedicine , Tissue Engineering
16.
J Am Chem Soc ; 143(31): 12315-12327, 2021 08 11.
Article in English | MEDLINE | ID: covidwho-1331364

ABSTRACT

Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.


Subject(s)
Dendrimers/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , RNA, Messenger/metabolism , Surface-Active Agents/chemistry , Animals , Dendrimers/chemical synthesis , Drug Carriers/chemical synthesis , Drug Liberation , Female , HEK293 Cells , Humans , Male , Mice , Proof of Concept Study , Surface-Active Agents/chemical synthesis
17.
Carbohydr Polym ; 269: 118345, 2021 Oct 01.
Article in English | MEDLINE | ID: covidwho-1271581

ABSTRACT

This work reports novel chitosan functionalized graphene oxide (GO) nanocomposites combined fluorescence imaging and therapeutic functions in one agent, which can serve as a promising alternative to alleviate related diseases caused hyperinflammation. Briefly, GO was designed to be conjugated with chitosan, fluorescein-labeled peptide, toll-like receptor 4 antibody and hydroxycamptothecin/aloe emodin. We have demonstrated that such nanocomposites could effectively achieve active targeted delivery of pro-apoptotic and anti-inflammatory drugs into inflammatory cells and cause cells apoptosis by acid-responsive drug release. Moreover, confocal fluorescence imaging confirms that the drug-induced inflammatory cells apoptosis could be visualized the light-up fluorescence of fluorescein activated by caspase-3. Meanwhile, inflammatory-related biomarkers have down-regulated after the nanocomposites' treatment in both vitro and vivo experiments consistent with the results in histological sections. In summary, the bifunctional nanocomposites that possess anti-inflammation and fluorescence imaging could serve as a promising therapeutic agent for reducing hyperinflammation caused by numerous diseases.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Apoptosis/physiology , Drug Carriers/chemistry , Inflammation/drug therapy , Nanocomposites/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Antibodies/immunology , Camptothecin/analogs & derivatives , Camptothecin/chemistry , Camptothecin/therapeutic use , Cattle , Cell Line , Chitosan/chemistry , Drug Liberation , Emodin/chemistry , Emodin/therapeutic use , Fluorescent Dyes/chemistry , Graphite/chemistry , Humans , Lipopolysaccharides , Mammary Glands, Human/drug effects , Mammary Glands, Human/pathology , Mastitis/chemically induced , Mastitis/drug therapy , Mastitis/pathology , Mice , Toll-Like Receptor 4/immunology
18.
Int J Mol Sci ; 22(13)2021 Jun 28.
Article in English | MEDLINE | ID: covidwho-1288899

ABSTRACT

Viral-associated respiratory infectious diseases are one of the most prominent subsets of respiratory failures, known as viral respiratory infections (VRI). VRIs are proceeded by an infection caused by viruses infecting the respiratory system. For the past 100 years, viral associated respiratory epidemics have been the most common cause of infectious disease worldwide. Due to several drawbacks of the current anti-viral treatments, such as drug resistance generation and non-targeting of viral proteins, the development of novel nanotherapeutic or nano-vaccine strategies can be considered essential. Due to their specific physical and biological properties, nanoparticles hold promising opportunities for both anti-viral treatments and vaccines against viral infections. Besides the specific physiological properties of the respiratory system, there is a significant demand for utilizing nano-designs in the production of vaccines or antiviral agents for airway-localized administration. SARS-CoV-2, as an immediate example of respiratory viruses, is an enveloped, positive-sense, single-stranded RNA virus belonging to the coronaviridae family. COVID-19 can lead to acute respiratory distress syndrome, similarly to other members of the coronaviridae. Hence, reviewing the current and past emerging nanotechnology-based medications on similar respiratory viral diseases can identify pathways towards generating novel SARS-CoV-2 nanotherapeutics and/or nano-vaccines.


Subject(s)
Antiviral Agents/chemistry , Drug Carriers/chemistry , Nanomedicine , Respiratory Tract Infections/pathology , Viral Vaccines/chemistry , Virus Diseases/pathology , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19/pathology , COVID-19/therapy , COVID-19/virology , Humans , Immune System/metabolism , Respiratory Tract Infections/therapy , Respiratory Tract Infections/virology , SARS-CoV-2/isolation & purification , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Virus Diseases/immunology , Virus Diseases/prevention & control , Virus Diseases/therapy
19.
Life Sci ; 280: 119744, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1281492

ABSTRACT

Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.


Subject(s)
Nanoparticles/chemistry , Polymers/chemistry , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , Vaccination , Viral Vaccines/administration & dosage , Animals , COVID-19/prevention & control , COVID-19/virology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Drug Carriers/chemistry , Humans , Influenza, Human/prevention & control , Influenza, Human/virology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/virology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Vaccination/methods , Viral Vaccines/therapeutic use
20.
J Mater Chem B ; 9(35): 6988-6993, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1262017

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an RNA virus-based disease that can be deadly. For critically ill patients, mechanical ventilation is an important life-saving treatment. However, mechanical ventilation shows a trade-off between supporting respiratory function and ventilator-induced lung injury (VILI). Surfactant therapy is a medical administration of exogenous surfactant to supplement or replace deficient or dysfunctional endogenous surfactant. Surfactant therapy can be used to postpone or shorten the use of mechanical ventilation to minimize or avoid VILI, because surfactants can reduce surface tension, improve lung compliance, and enhance oxygenation. In addition, nanotechnology can be applied to improve the therapeutic effect and reduce the adverse effects of surfactants. In this perspective, we discussed how nanoparticles deliver surfactants through intravenous injection and inhalation to the expected lung disease regions where surfactants are mostly needed, and discussed the prospects of nanoparticle-mediated surfactant therapy in the treatment of patients with severe COVID-19.


Subject(s)
COVID-19/drug therapy , Drug Carriers/chemistry , Nanoparticles/chemistry , Pulmonary Surfactants/therapeutic use , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Injections, Intravenous , Lung , Nanoparticles/administration & dosage , Pulmonary Surfactants/administration & dosage , Pulmonary Surfactants/chemistry , SARS-CoV-2
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