Periodic Reporting for period 2 - NanoCarb (Glyco-Nanoparticles for Applications in Advance Nanomedicine )
Período documentado: 2020-10-01 hasta 2023-03-31
The use of nanoparticles (NPs) of 100 nm or smaller in nanomedicine has rapidly increased in the last decades. In particular, NPs of different sizes and chemical compositions are routinely synthesised in many research laboratories in academia and industries. Frequently, they are surface grafted with targeting molecules or antibodies to increase their therapeutic targeting properties. NPs can be loaded with insoluble drugs to facilitate a selective drug release in the target tissue and increase the therapeutic index and decrease side effects. Recently NPs have been successfully tested in the development of vaccines. NPs also have great potential as contrast agents and in different therapies using the material's physical properties like photothermal, photodynamics, etc. Despite the numerous and exciting research findings, the area of nanomedicine suffers from several barriers, causing translation from the research laboratories to clinical products to be significantly lower than expected. This is due to several challenges and unexpected factors at the bio/nano interface that influences NPs' efficacy in clinical use and their low accumulation in the target tissue as well as the change of their physicochemical properties and interaction with biological receptors and cells after exposure to biological fluid.
Glycans or sugars are highly abundant molecules found in nature, and they have exploitable properties that make them unique candidates for implementation in the nanotechnology field. They are highly hydrophilic and when used for NP functionalization keep the NP surface hydrated, they can carry a charge and increase the NP colloidal stability, and they can attenuate the unspecific interactions with proteins present in the biological environment. They are also highly biocompatible and biodegradable, and they can be produced on a large scale. Glycans and oligo-saccharides also have a well-defined chemical structure that can be modified and facilitate a direct conjugation on other polymers or linkers.
In NanoCarb we have selected a set of glycans that are either synthesised or purified from biological matrixes. They are used to produce stable Glyco-NP complexes that have specific properties, including increased biocompatibility, increased targeting and but can also be used as devices for in vitro diagnostics. NanoCarb has developed a complete platform for the Glyco-NP synthesis and characterisation that ensure that the glycans are biologically active and available for biological targeting in the biological milieu. The synthesised particles are tested in parallel for in vitro biocompatibility and binding ability. This approach created a loop of continuous feedback between NP synthesis and testing. The most promising and non-toxic Glyco-NP were selected and tested for in vivo studies to assess their efficacy.
The main objective of NanoCarb has been to provide a unique training experience through research, training and exchange, of 15 early-stage researchers in the field of nanotechnology and carbohydrate chemistry and in vitro/ in vivo testing. Nanotechnology is a highly multidisciplinary subject, and there is a clear need for a broad training structure with selected content for young researchers who will become future leaders in nanomedicine. The structure of the consortium allowed a broad and comprehensive training programme in academia, industry and research centres where the researchers are exposed to a dynamic environment. This innovative environment will provide unique training to the Early Stage Researchers, making them highly competitive scientists with competitive CVs for industry or academia.
Glycans or sugars are highly abundant molecules found in nature, and they have exploitable properties that make them unique candidates for implementation in the nanotechnology field. They are highly hydrophilic and when used for NP functionalization keep the NP surface hydrated, they can carry a charge and increase the NP colloidal stability, and they can attenuate the unspecific interactions with proteins present in the biological environment. They are also highly biocompatible and biodegradable, and they can be produced on a large scale. Glycans and oligo-saccharides also have a well-defined chemical structure that can be modified and facilitate a direct conjugation on other polymers or linkers.
In NanoCarb we have selected a set of glycans that are either synthesised or purified from biological matrixes. They are used to produce stable Glyco-NP complexes that have specific properties, including increased biocompatibility, increased targeting and but can also be used as devices for in vitro diagnostics. NanoCarb has developed a complete platform for the Glyco-NP synthesis and characterisation that ensure that the glycans are biologically active and available for biological targeting in the biological milieu. The synthesised particles are tested in parallel for in vitro biocompatibility and binding ability. This approach created a loop of continuous feedback between NP synthesis and testing. The most promising and non-toxic Glyco-NP were selected and tested for in vivo studies to assess their efficacy.
The main objective of NanoCarb has been to provide a unique training experience through research, training and exchange, of 15 early-stage researchers in the field of nanotechnology and carbohydrate chemistry and in vitro/ in vivo testing. Nanotechnology is a highly multidisciplinary subject, and there is a clear need for a broad training structure with selected content for young researchers who will become future leaders in nanomedicine. The structure of the consortium allowed a broad and comprehensive training programme in academia, industry and research centres where the researchers are exposed to a dynamic environment. This innovative environment will provide unique training to the Early Stage Researchers, making them highly competitive scientists with competitive CVs for industry or academia.
Despite the COVID-19 restrictions, within the whole consortium, we have synthesised three different types of NP that have been functionalised with several synthetic glycans or with two types of complex glycans isolated from a biological matrix. The newly developed glycol-NPs have been tested using multiple approaches, to assess their binding capacity towards targeted molecules, and to tune the NP-physical chemical properties with their binding efficacy. Lastly, the in vivo testing groups have developed multiple qualitative and quantitative approaches to visualise the NP after exposure, which provides crucial information on the NP biodistribution in animal models.
It is clear that the use of nanomaterials in healthcare applications can offer pragmatic and simple solutions to develop new pharmaceutical therapeutics that could be used for challenging diseases. For example, Pfizer and Moderna have developed, in a time-efficient manner, the first vaccines against COVID-19 that use biocompatible solid lipid NPs to deliver inside the cell mRNA messengers for the transcription and cellular production of the viral spike protein to develop a humoral immune response to the virus in case of future infection. In Nanocarb, we have extensively studied several strategies to conjugate glycans on different polymers to enhance their targeting efficacy and control the biomolecular corona formation. Additionally, we have successfully integrated different techniques for high-resolution characterisation of the conjugated materials and to predict their biological fate also in a cell-free condition. Additionally, the nanomaterials were tested after exposure to complex biological fluids to evaluate changes in their physicochemical properties and targeting properties.
The research that is carried out in the NanoCarb consortium contributed to the development of a testing platform for effective and safe nanoparticles for healthcare applications (including chronic diseases like cancer) and trained young researchers in different research topics which are essential if working in the field of nanotechnology.
The research that is carried out in the NanoCarb consortium contributed to the development of a testing platform for effective and safe nanoparticles for healthcare applications (including chronic diseases like cancer) and trained young researchers in different research topics which are essential if working in the field of nanotechnology.