Periodic Reporting for period 1 - SEE (MAPPING THE SKIN-IMMUNE INTERACTIONS OF NOVEL 2D MATERIALS: MXENES)
Período documentado: 2021-07-01 hasta 2023-06-30
The Marie Skłodowska Curie Action (MSCA) Global Fellowship “Mapping the skin-immune interactions of novel 2D materials: MXenes” (SEE) aims to provide a thorough evaluation of the skin impact and possible immunomodulation of a wide variety of the new two-dimensional (2D) nanomaterials transition metal carbides/carbonitrides (MXenes).
MXenes are emergent 2D materials with a wide variety of structures and compositions. To promote the Safe and Healthy use of ‘Future and Emerging Technologies’, such as the innovative 2D materials MXenes, studying their biocompatibility and immunomodulatory effects upon skin exposure is of fundamental importance. Indeed, cutaneous exposure represents one of the main exposure routes to nanomaterials during their production, but also for translational medicine and nanotechnology applications, in particular those requiring cutaneous contact. In this view, the prospect of biomedical tools, including skin cancer theranostics and wound healing tools, as well as wearable or implantable bioelectronics using MXenes, has gained traction. However, there is a paucity of data on the impact of MXene at the skin and immune level. No study was able to provide a broad picture of the cutaneous impact and the related immunological effects of a wide variety of well-characterized MXenes, exploring the immune interactions of several immune cell populations with the materials. To date, no research group has provided a harmonized cutting-edge method for the classification of MXenes based not only on their chemical and physical characteristics but also on their skin immunological responses and potential immunotoxicity.
The overall goal of the project is to overcome the aforementioned limits of conventional skin nano-immunotoxicology approaches and knowledge, providing a comprehensive picture of MXene skin immunology in relation to the structural properties (e.g. shape, size, functionalization, etc.) of the materials. Therefore it is critical to provide an innovative library of MXenes in relation not only to their physicochemical properties but also to their skin-immune interactions, investigating the potential molecular mechanisms underlying their impact at the cutaneous level.
To this end, the SEE project aims to i) synthesize and characterize MXenes with different physical and chemical properties; ii) evaluate MXene cutaneous compatibility and immune profiling, and iii) correlate skin-immune phenotype with MXene physicochemical properties.
Within SEE, the Fellow will introduce her own novel concept of “Nano-SkinImmunity-by-design”, where the analysis of the cutaneous effects when designing MXenes (and 2D materials) will not only be relevant for their safety but will also turn them into active tools for cutaneous applications endowed of immune properties, tailorable adjusting their physicochemical profile. By exploring these crucial aspects, SEE aims at incising the strategic field of MXenes and 2D materials as well as their role in biomedicine and nanotechnology at the European level and beyond
MXenes are emergent 2D materials with a wide variety of structures and compositions. To promote the Safe and Healthy use of ‘Future and Emerging Technologies’, such as the innovative 2D materials MXenes, studying their biocompatibility and immunomodulatory effects upon skin exposure is of fundamental importance. Indeed, cutaneous exposure represents one of the main exposure routes to nanomaterials during their production, but also for translational medicine and nanotechnology applications, in particular those requiring cutaneous contact. In this view, the prospect of biomedical tools, including skin cancer theranostics and wound healing tools, as well as wearable or implantable bioelectronics using MXenes, has gained traction. However, there is a paucity of data on the impact of MXene at the skin and immune level. No study was able to provide a broad picture of the cutaneous impact and the related immunological effects of a wide variety of well-characterized MXenes, exploring the immune interactions of several immune cell populations with the materials. To date, no research group has provided a harmonized cutting-edge method for the classification of MXenes based not only on their chemical and physical characteristics but also on their skin immunological responses and potential immunotoxicity.
The overall goal of the project is to overcome the aforementioned limits of conventional skin nano-immunotoxicology approaches and knowledge, providing a comprehensive picture of MXene skin immunology in relation to the structural properties (e.g. shape, size, functionalization, etc.) of the materials. Therefore it is critical to provide an innovative library of MXenes in relation not only to their physicochemical properties but also to their skin-immune interactions, investigating the potential molecular mechanisms underlying their impact at the cutaneous level.
To this end, the SEE project aims to i) synthesize and characterize MXenes with different physical and chemical properties; ii) evaluate MXene cutaneous compatibility and immune profiling, and iii) correlate skin-immune phenotype with MXene physicochemical properties.
Within SEE, the Fellow will introduce her own novel concept of “Nano-SkinImmunity-by-design”, where the analysis of the cutaneous effects when designing MXenes (and 2D materials) will not only be relevant for their safety but will also turn them into active tools for cutaneous applications endowed of immune properties, tailorable adjusting their physicochemical profile. By exploring these crucial aspects, SEE aims at incising the strategic field of MXenes and 2D materials as well as their role in biomedicine and nanotechnology at the European level and beyond
Work performed during this fellowship lead to the following main results:
i) The training delivery on fabrication, characterization, handling, and manipulation of MXenes was completed and allowed acquiring new knowledge and expertise in Material Science, resulting in the production of a panel of MXenes with different physical and chemical properties.
ii) Several factors were considered when synthesizing MXenes, including the concentration of hydrofluoric acid (HF) or mixture (LiF or NaF + HCl), etching temperature, and time. Moreover, the delamination of multilayered MXene powders was performed with a choice of intercalants. Production of MXenes with different delamination methods was obtained.
iii) The characterization of all MXenes was completed. MXenes were thoroughly characterized by complementary spectroscopic and microscopic techniques.
iv) The effects of a panel of MXenes with different physical and chemical properties were evaluated on immune cells. Results were obtained beyond the envisaged objectives, by developing a versatile multiplexed label-free single-cell detection strategy based on CyTOF and MIBI-TOF for MXenes. This strategy enables nanomaterial detection and simultaneous measurement of multiple cell and tissue features, enabling new opportunities in biomedicine.
i) The training delivery on fabrication, characterization, handling, and manipulation of MXenes was completed and allowed acquiring new knowledge and expertise in Material Science, resulting in the production of a panel of MXenes with different physical and chemical properties.
ii) Several factors were considered when synthesizing MXenes, including the concentration of hydrofluoric acid (HF) or mixture (LiF or NaF + HCl), etching temperature, and time. Moreover, the delamination of multilayered MXene powders was performed with a choice of intercalants. Production of MXenes with different delamination methods was obtained.
iii) The characterization of all MXenes was completed. MXenes were thoroughly characterized by complementary spectroscopic and microscopic techniques.
iv) The effects of a panel of MXenes with different physical and chemical properties were evaluated on immune cells. Results were obtained beyond the envisaged objectives, by developing a versatile multiplexed label-free single-cell detection strategy based on CyTOF and MIBI-TOF for MXenes. This strategy enables nanomaterial detection and simultaneous measurement of multiple cell and tissue features, enabling new opportunities in biomedicine.
Within the project, different interesting results were identified.
- Considering the critical unmet need to detect and image 2D materials within single cells and tissues while surveying a high degree of information from single samples, the project proposed a versatile multiplexed label-free single-cell detection strategy based on CyTOF and MIBI-TOF. This strategy enabled nanomaterial detection and simultaneous measurement of multiple cell and tissue features. As a proof of concept, a set of MXenes were selected to ensure mass detection within the cytometry range. Together with the detection, mass cytometry we used to capture several biological aspects of MXenes, such as their biocompatibility and cytokine production after their uptake. In vivo biodistribution experiments in mice confirmed the versatility of the detection strategy and revealed MXene accumulation in the liver, blood, spleen, lungs and relative immune cell subtypes. The label-free detection of 2D materials by mass cytometry at the single-cell level, on multiple cell subpopulations, and in multiple organs simultaneously, is expected to enable exciting new opportunities in biomedicine.
- Within the project, MXenes with different characteristics were developed and the material physicochemical properties were correlated to their biological impact with a particular focus on immune cells, including macrophages and peripheral blood mononuclear cells.
- The advanced approach and analysis methodology can be applied to other kinds of nanostructures and nanomaterials with similar properties.
- Several companies interested in the SEE project results have been identified. These have been targeted by different communication and dissemination actions and networking/clustering activities.
- The safe use of MXenes will be beneficial not only for their biomedical applications, but also for other sectors where MXenes are emerging as promising candidates, from energy storage, catalysis, and nanoelectronics, to communications and sensing.
- Understanding the effects and customizing the design of MXenes with tunable properties is expected to paw the way for a wide variety of new opportunities and discoveries for MXene technologies in several fields.
- The results will accelerate the rapid and safe adoption of newly developed materials, also facilitating general public awareness and trust in 2D material advances.
- The findings can potentially contribute to the efforts of regulatory agencies in developing specific guidelines for nanomaterial safety assessment.
- In addition, by exploring the biological impact of MXenes and shade light on their classification, the project is expected to facilitate the application-oriented design of MXenes making it possible to scale up MXene synthesis well past laboratory scales, and potentially providing a path toward the direct commercialization of MXene and MXene-based technologies.
- Considering the critical unmet need to detect and image 2D materials within single cells and tissues while surveying a high degree of information from single samples, the project proposed a versatile multiplexed label-free single-cell detection strategy based on CyTOF and MIBI-TOF. This strategy enabled nanomaterial detection and simultaneous measurement of multiple cell and tissue features. As a proof of concept, a set of MXenes were selected to ensure mass detection within the cytometry range. Together with the detection, mass cytometry we used to capture several biological aspects of MXenes, such as their biocompatibility and cytokine production after their uptake. In vivo biodistribution experiments in mice confirmed the versatility of the detection strategy and revealed MXene accumulation in the liver, blood, spleen, lungs and relative immune cell subtypes. The label-free detection of 2D materials by mass cytometry at the single-cell level, on multiple cell subpopulations, and in multiple organs simultaneously, is expected to enable exciting new opportunities in biomedicine.
- Within the project, MXenes with different characteristics were developed and the material physicochemical properties were correlated to their biological impact with a particular focus on immune cells, including macrophages and peripheral blood mononuclear cells.
- The advanced approach and analysis methodology can be applied to other kinds of nanostructures and nanomaterials with similar properties.
- Several companies interested in the SEE project results have been identified. These have been targeted by different communication and dissemination actions and networking/clustering activities.
- The safe use of MXenes will be beneficial not only for their biomedical applications, but also for other sectors where MXenes are emerging as promising candidates, from energy storage, catalysis, and nanoelectronics, to communications and sensing.
- Understanding the effects and customizing the design of MXenes with tunable properties is expected to paw the way for a wide variety of new opportunities and discoveries for MXene technologies in several fields.
- The results will accelerate the rapid and safe adoption of newly developed materials, also facilitating general public awareness and trust in 2D material advances.
- The findings can potentially contribute to the efforts of regulatory agencies in developing specific guidelines for nanomaterial safety assessment.
- In addition, by exploring the biological impact of MXenes and shade light on their classification, the project is expected to facilitate the application-oriented design of MXenes making it possible to scale up MXene synthesis well past laboratory scales, and potentially providing a path toward the direct commercialization of MXene and MXene-based technologies.