2D MXenes with antiviral and immunomodulatory properties: A pilot study against SARS-CoV-2

Abstract

Two-dimensional transition metal carbides/carbonitrides known as MXenes are rapidly growing as multimodal nanoplatforms in biomedicine. Here, taking SARS-CoV-2 as a model, we explored the antiviral properties and immune-profile of a large panel of four highly stable and well-characterized MXenes - Ti 3 C 2 T x , Ta 4 C 3 T x , Mo 2 Ti 2 C 3 T x and Nb 4 C 3 T x . To start with antiviral assessment, we first selected and deeply analyzed four different SARS-CoV-2 genotypes, common in most countries and carrying the wild type or mutated spike protein. When inhibition of the viral infection was tested in vitro with four viral clades, Ti 3 C 2 T x in particular, was able to significantly reduce infection only in SARS-CoV-2/clade GR infected Vero E6 cells. This difference in the antiviral activity, among the four viral particles tested, highlights the importance of considering the viral genotypes and mutations while testing antiviral activity of potential drugs and nanomaterials. Among the other MXenes tested, Mo 2 Ti 2 C 3 T x also showed antiviral properties. Proteomic, functional annotation analysis and comparison to the already published SARS-CoV-2 protein interaction map revealed that MXene-treatment exerts specific inhibitory mechanisms. Envisaging future antiviral MXene-based drug nano-formulations and considering the central importance of the immune response to viral infections, the immune impact of MXenes was evaluated on human primary immune cells by flow cytometry and single-cell mass cytometry on 17 distinct immune subpopulations. Moreover, 40 secreted cytokines were analyzed by Luminex technology. MXene immune profiling revealed i) the excellent bio and immune compatibility of the material, as well as the ability of MXene ii) to inhibit monocytes and iii) to reduce the release of pro-inflammatory cytokines, suggesting an anti-inflammatory effect elicited by MXene. We here report a selection of MXenes and viral SARS-CoV-2 genotypes/mutations, a series of the computational, structural and molecular data depicting deeply the SARS-CoV-2 mechanism of inhibition, as well as high dimensional single-cell immune-MXene profiling. Taken together, our results provide a compendium of knowledge for new developments of MXene-based multi-functioning nanosystems as antivirals and immune-modulators.

2D MXenes for combatting COVID-19 Pandemic: A perspective on latest developments and innovations

“…are some of the examples of synthesized MXenes from which the Ti 3 C 2 T x is the most explored one [26] . Till now more than 30 MXenes have been synthesized and more than 100 MXene stoichiometries have been predicted by simulations, making them one of the largest families of 2D materials [17] . The double transition metal MXenes are comprised of two transition metal atoms as compared to mono transition metal MXenes [27] .…”

“…Researchers have reported the missense mutation in the SARS-CoV-2 spike protein D614G as the predominant clade of viral infection in most countries, due to its greater binding affinity to ACE2 receptors, efficient cellular entry, and minimal antibody interactions [66] , [67] , [68] . This mutation has been found mostly in the GH and GR clades of the SARS-CoV-2 virus, making it more promising for the faster spreading of infection [17] .…”

“… MXene properties MXene based prevention and diagnosis of COVID-19 Ref. 1 Photocatalytic Virus inactivation [13] 2 Photothermal Virus inactivation [14] 3 Antiinflammatory Vaccine and drug delivery [17] 4 Adsorption Removal of contaminants [33] 5 Amino acid adsorption Trapping of virus [72] 6 Modification of spike protein Hindrance of virus life cycle [73] 7 Histocompatibility Reduced cytotoxicity [82] 8 Photoacoustic imaging Diagnosis of internal organs [84] 9 Urea Adsorption Dialyzer [107] 10 Porous structure Fabrication of face masks [112] 11 Sensing Biosensor (detection of biomarkers) [123] 12 Viscoelasticity 3D printed biomedical instruments [129] …”

“…The greater drug loading and point-specific drug release capacity of MXene can be utilized for delivering the drug in remote parts of the internal organs of COVID-19 patients [16] . Along with these, the greater biocompatibility and lesser cytotoxicity of MXene reduce the risk of poisoning as seen in the case of other advanced materials [17] .…”

Fabrication of Smart Tantalum Carbide MXene Quantum Dots with Intrinsic Immunomodulatory Properties for Treatment of Allograft Vasculopathy

“…[ 16 ] In particular, MXene‐based approaches are being developed to treat refractory inflammatory conditions and suppress rejection of transplanted tissue constructs. [ 11,16 ] However, the long‐term bioinertness of titanium‐based materials has since been called into question. [ 17,18 ] In fact, several reports on the cytotoxicity of Ti 3 C 2 T x MXene at medium‐to‐high concentrations raised significant concern on the eventual clinical translatability of these materials.…”