Periodic Reporting for period 1 - Micro4Nano (Multifunctional nanocarriers for nonlinear microscopy: new tools for biology and medicine)
Reporting period: 2021-10-01 to 2024-09-30
Multifunctional Nanocarriers for Nonlinear Microscopy: New Tools for Biology and Medicine (Micro4Nano)
Micro4Nano promotes the career development of early-stage and experienced researchers by offering advanced training opportunities in 11 academic and 2 non-academic (SMEs) research laboratories distributed across 10 countries in Europe (Croatia, Finland, France, Italy, Poland, Spain) and abroad (Argentina, Brazil, Israel, Malaysia, USA). The project proposes an ambitious research agenda aimed at establishing and optimizing new tools, materials, and techniques for the 3D visualization of thick biological tissues. Micro4Nano technology will be validated in advanced biomedical and drug delivery applications, but it holds enormous potential for wider applications in materials science, biology, and beyond.
The project’s primary goal is to address four challenging technical objectives (TOs) that must be met simultaneously to achieve the 3D functional imaging of thick tissues. This imaging will extract reliable information about tissue structure, biochemical composition, and function:
TO1: Design and production of innovative fluorescent nanocarriers, developed through various molecular and supramolecular synthetic strategies. These will be characterized and optimized using powerful optical spectroscopy and theoretical chemistry tools.
TO2: Multiphoton microscopy of ex vivo animal tissues for real-time monitoring of large tissue areas (up to 1-2 mm in depth). Techniques such as multicolor detection, FRET microscopy, and spectrally resolved imaging (hyperspectral microscopy) will be used to extract complete data on tissue function and structure.
TO3: Development of new microfluidic systems for maintaining the vitality of cells/tissues and for real-time bioimaging using multiphoton and Raman microscopy.
TO4: Validation of materials and methods in drug delivery and nanomedicine applications. Multifunctional nanocarriers, loaded with anti-inflammatory drugs and fluorescent labels, will be tested in advanced drug-delivery studies on ex vivo animal tissues. These will allow monitoring of the distribution and diffusion of nanocarriers and their functional cargo within tissue, with assessments carried out on their impact on cells and tissues in microfluidic systems under a microscope.
The research conducted within the Micro4Nano project has the potential to significantly advance biomedical science and medicine, with broad implications for society. The development of novel imaging tools, such as those based on multifunctional nanocarriers, will enable deeper, more accurate investigations of biological tissues. This could revolutionize our understanding of diseases, such as cancer and neurological disorders, where current imaging techniques are limited in depth and resolution. Furthermore, these new technologies will improve the precision of drug delivery systems, reducing side effects and improving the efficacy of treatments. The integration of cutting-edge imaging and microfluidic technologies will not only drive advances in drug development but will also facilitate the creation of personalized medicine solutions. In the long term, these advancements could lead to improved patient outcomes, more efficient healthcare systems, and ultimately, better quality of life for individuals worldwide.
Micro4Nano promotes the career development of early-stage and experienced researchers by offering advanced training opportunities in 11 academic and 2 non-academic (SMEs) research laboratories distributed across 10 countries in Europe (Croatia, Finland, France, Italy, Poland, Spain) and abroad (Argentina, Brazil, Israel, Malaysia, USA). The project proposes an ambitious research agenda aimed at establishing and optimizing new tools, materials, and techniques for the 3D visualization of thick biological tissues. Micro4Nano technology will be validated in advanced biomedical and drug delivery applications, but it holds enormous potential for wider applications in materials science, biology, and beyond.
The project’s primary goal is to address four challenging technical objectives (TOs) that must be met simultaneously to achieve the 3D functional imaging of thick tissues. This imaging will extract reliable information about tissue structure, biochemical composition, and function:
TO1: Design and production of innovative fluorescent nanocarriers, developed through various molecular and supramolecular synthetic strategies. These will be characterized and optimized using powerful optical spectroscopy and theoretical chemistry tools.
TO2: Multiphoton microscopy of ex vivo animal tissues for real-time monitoring of large tissue areas (up to 1-2 mm in depth). Techniques such as multicolor detection, FRET microscopy, and spectrally resolved imaging (hyperspectral microscopy) will be used to extract complete data on tissue function and structure.
TO3: Development of new microfluidic systems for maintaining the vitality of cells/tissues and for real-time bioimaging using multiphoton and Raman microscopy.
TO4: Validation of materials and methods in drug delivery and nanomedicine applications. Multifunctional nanocarriers, loaded with anti-inflammatory drugs and fluorescent labels, will be tested in advanced drug-delivery studies on ex vivo animal tissues. These will allow monitoring of the distribution and diffusion of nanocarriers and their functional cargo within tissue, with assessments carried out on their impact on cells and tissues in microfluidic systems under a microscope.
The research conducted within the Micro4Nano project has the potential to significantly advance biomedical science and medicine, with broad implications for society. The development of novel imaging tools, such as those based on multifunctional nanocarriers, will enable deeper, more accurate investigations of biological tissues. This could revolutionize our understanding of diseases, such as cancer and neurological disorders, where current imaging techniques are limited in depth and resolution. Furthermore, these new technologies will improve the precision of drug delivery systems, reducing side effects and improving the efficacy of treatments. The integration of cutting-edge imaging and microfluidic technologies will not only drive advances in drug development but will also facilitate the creation of personalized medicine solutions. In the long term, these advancements could lead to improved patient outcomes, more efficient healthcare systems, and ultimately, better quality of life for individuals worldwide.
So far, Micro4Nano has implemented 40 secondments (overall around 79 person months), involving 35 reaserchers. All Beneficiaries and Partners were involved in the project, and contributed in implementing the secondments by hosting and or sending researchers. 18 papers have pubblished in peer review journal, as open access publications.
The main results of the first three years of the project are the following:
1) identification of fluorescent dyes for functional imaging and/or for loading in different types of nanocarriers
2) preparation and characterization of fluorescent nanovescicles, decorated with different dyes and/or targeting agents for biomaging
3) 3D imaging of ocular and skin animal tissues, stained with dye-loaded micelles for drug-delivery
4) development and application of theoretical protocols for the charaterization of dyes and nanoparticle
5) development of the PMMA DEVICE STATION: From mold development to high resolution PMMA chip fabrication (https://www.elveflow.com/microfluidics-beta-innovation/beta-packs/pmma-device-station/(opens in new window))
6) A comparative review of medium recirculation system setups (https://microfluidics-innovation-center.com/reviews/comparative-review-medium-recirculation-system-setups/(opens in new window))
The main results of the first three years of the project are the following:
1) identification of fluorescent dyes for functional imaging and/or for loading in different types of nanocarriers
2) preparation and characterization of fluorescent nanovescicles, decorated with different dyes and/or targeting agents for biomaging
3) 3D imaging of ocular and skin animal tissues, stained with dye-loaded micelles for drug-delivery
4) development and application of theoretical protocols for the charaterization of dyes and nanoparticle
5) development of the PMMA DEVICE STATION: From mold development to high resolution PMMA chip fabrication (https://www.elveflow.com/microfluidics-beta-innovation/beta-packs/pmma-device-station/(opens in new window))
6) A comparative review of medium recirculation system setups (https://microfluidics-innovation-center.com/reviews/comparative-review-medium-recirculation-system-setups/(opens in new window))
We aim to develop new fluorescent nanocarriers optimized for the functional imaging of biological tissues and for drug delivery. These nanocarriers will be loaded with dyes, drugs, targeting agents, and other functional components to combine multiple functionalities within a single carrier. The 3D imaging of ocular and skin tissues will be further explored, and extended to include nasal mucosa. Additionally, various types of microfluidic chips will be tested for cell cultures.
The primary impact of the project lies in the development of new materials (functional nanocarriers) and techniques (multiphoton imaging and microfluidics) for drug delivery and biomedicine.
Beyond the scientific impact, Micro4Nano will significantly influence the careers of the researchers involved in the secondments, especially early-stage researchers, who will gain valuable experience working in an international, multidisciplinary, and intersectoral environment.
The primary impact of the project lies in the development of new materials (functional nanocarriers) and techniques (multiphoton imaging and microfluidics) for drug delivery and biomedicine.
Beyond the scientific impact, Micro4Nano will significantly influence the careers of the researchers involved in the secondments, especially early-stage researchers, who will gain valuable experience working in an international, multidisciplinary, and intersectoral environment.