Periodic Reporting for period 1 - NanoCarb (Glyco-Nanoparticles for Applications in Advance Nanomedicine )
Período documentado: 2018-10-01 hasta 2020-09-30
The use of nanoparticles (NP) of 100nm or smaller in diameter in nanomedicine, has rapidly increased in the last 20 years. In particular, NP of different sizes and materials are routinely synthesised in many research laboratories either in academia on in industries, and their surface can be grafted with targeting molecules or antibodies to increase the targeting properties. NP can either be loaded with insoluble drugs to increase a selective drug release in the target and increase the therapeutic effect and decrease the side effect and recently NPs have been successfully tested in the development of vaccines. NPs also have great potentials to be used as contrast agents and in photothermal therapy. Despite the numerous and exciting research findings, the area of nanomedicine suffers from several drawbacks, and the translation from the research laboratories to clinical products is significantly lower than the expected pace. This is due to several challenges and unexpected factors at the bio/nano interface that influences nanoparticles (NPs) efficacy in clinical use and their low accumulation in the affected area and also the change of their physico-chemical properties and interaction with biological receptors and cells after exposure in biological fluid.
Glycans or sugar are highly abundant proteins found in nature, and they have exploitable properties that make them unique candidates to implement the nanotechnology field. They are highly hydrophilic and 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 are 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, and they are used to form stable Glyco-NP complexes that have specific properties, including increased biocompatibility, increased targeting and 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 also in the biological milieu and the synthesised particles are tested in parallel for in vitro biocompatibility and binding assay. 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 is 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 that will become future leaders in nanomedicine. The structure of the consortium allows 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 researcher, and they will make them highly competitive scientists that will have the potential to be hired in industry or academia.
Glycans or sugar are highly abundant proteins found in nature, and they have exploitable properties that make them unique candidates to implement the nanotechnology field. They are highly hydrophilic and 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 are 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, and they are used to form stable Glyco-NP complexes that have specific properties, including increased biocompatibility, increased targeting and 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 also in the biological milieu and the synthesised particles are tested in parallel for in vitro biocompatibility and binding assay. 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 is 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 that will become future leaders in nanomedicine. The structure of the consortium allows 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 researcher, and they will make them highly competitive scientists that will have the potential to be hired in industry or academia.
Despite the COVID-19 restrictions, within the whole consortium, we have synthesised three different types of NP that have currently 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 test their binding capacity towards targeted molecules, 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, that provide crucial information on the NP biodistribution that Is in full compliance with the 3Rs.
It is clear that nanoparticles can offer pragmatic and simple solutions and 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 uses biocompatible nanoparticles that protect and enhance the cellular uptake of mRNA or saRNA.
Similarly, in NanoCarb we are developing a new generation of safe and biocompatible and non-toxic glyco-nanoparticles that have the potential to be used in chronic diseases, including cancer. The research that is carried out in the NanoCarb consortium will contribute to the development of a testing platform for effective and safe nanoparticles for healthcare application but also to the training of young researchers in nanomedicine.
Similarly, in NanoCarb we are developing a new generation of safe and biocompatible and non-toxic glyco-nanoparticles that have the potential to be used in chronic diseases, including cancer. The research that is carried out in the NanoCarb consortium will contribute to the development of a testing platform for effective and safe nanoparticles for healthcare application but also to the training of young researchers in nanomedicine.