Final Report Summary - NANOBIOSACCHARIDES (Nanotechnologies for Bio-inspired polySaccharides: biological decoys designed as knowledge-based, multifunctional biomaterials)
The 'Nanotechnologies for bio-inspired polysaccharides: biological decoys designed as knowledge-based, multifunctional biomaterials' (NANOBIOSACCHARIDES) set out to develop and exploit nanotechnologies for knowledge-based, multi-functional, bio-inspired polysaccharides to be used as intelligent, sustainable, environment-friendly, consumer- and patient-safe bio-materials.
The NANOBIOSACCHARIDES project was based on the novel concept of biological decoys. A decoy is inspired by a natural material, but it does not simply copy it. A decoy resembles a natural structure partially, but it does not mimic it completely. Therefore, it may elicit only those aspects of a given natural reaction that are wanted, with no unwanted side reactions.
The NANOBIOSACCHARIDES project aimed at developing biological decoys based on naturally occurring polysaccharides. Polysaccharides, the most versatile and diverse class of biopolymers, have long been known to be information bearing molecules, but we lack a detailed molecular understanding of their biological activities. Their great complexity, diversity, and innate microheterogeneity make analysis and synthesis extremely demanding.
However, the emerging techniques of nanotechnology promise to allow analysis and manipulation at a molecular, nano-scale, and, possibly, single molecule level. The NANOBIOSACCHARIDES project has established cause-consequence links between the physico-chemical properties of polysaccharides, in particular of chitosans, in solution or as a nanosystem, and their biological activities.
Chitosan is an extremely versatile biopolymer with potential applications in the material and life sciences. However, the diverse life science applications - in fields such as medical biomaterials, drug and gene delivery, cell and tissue engineering, cosmeceutics, food technology, and agriculture - suffer from poor reproducibility of the effects observed.
The project partners have argued that this may at least partly be due to batch-to-batch differences in the insufficiently characterised chitosans commercially available today. The NANOBIOSACCHARIDES project focused on medical and pharmacological applications of nano-scale characterised chitosans as well as chitosan-based nanoparticles and physical hydrogels.
The chitosans, nanoparticles, and hydrogels were generated using advanced chemical and enzymatic procedures with known modes of action, yielding products with defined physico-chemical properties and biological activities. An in depth understanding of the structure-function relationships of biologically active polysaccharides will allow the development of nanoparticles made from decoy chitosans able to overcome biological barriers and to facilitate the delivery of complex drugs such as insulin via nasal, pulmonary, or oral routes instead of direct injection into the blood vessels.
Similarly, nano-structured physical hydrogels made from decoy chitosans will eventually allow to generate a suitable interface between biomaterial and living tissue, promising the generation of wound dressings under which the scar-free development of new skin tissue is induced. The NANOBIOSACCHARIDES project allowed an enlargement of the consortium by inclusion of selected international partners. This strengthened the aspect of enzymatic generation and analysis of chitosans with other than random patterns of acetylation with potential novel physico-chemical properties and biological functionalities. At the same time, the new partners also widenened the focus of the project to include other promising applications, such as in agricultural plant disease protection, and in skin-whitening cosmeceutics.
Not unexpectedly, the different areas of our project developed differently, some towards more basic research, some towards more applied development:
- One branch of the project took a more basic approach to understanding the physico-chemistry of polysaccharide solution properties and their involvement in spontaneous formation of nanoparticles, resulting in the formulation of a universal law of behaviour for polyelectrolyte polysaccharides in aqueous solutions. This now allows us to understand the continuum of polysaccharide solutions, nanoparticles, and physical hydrogels - and this will in the long run allow the development of reliable, knowledge-based applications.
- Another branch of the project took a more applied approach towards optimising the biological properties of polysaccharide nanoparticles by varying their compositions and mode of preparation, comparing their bio-compatibilities and their abilities to serve as drug, gene, or vaccine carriers for different types of human and animal cells. The results allowed us to identify the most promising types of nanoparticles for different potential applications.
The scope and reach of the NANOBIOSACCHARIDES project was widened to include cosmetics and agricultural applications, and both fields profited greatly from the fundamental and applied work done on nanoparticle formation and bio-compatibility so that further research strategies and potential avenues into markets were identified and defined.
Similarly, the work on enzymatic nanostructuring of polysaccharides, though it proved more difficult and time consuming than initially envisaged, finally led to proof of principle that the biological activities and potentially even the physico-chemical properties of polysaccharides are dependent on their nanostructure, namely on their patterns of substitution. This insight opened up a whole new area of research with enormous economic potential, mostly in the medical and food market sectors, which will be pursued in a follow-up European research project with strong industrial participation.
Overall, the NANOBIOSACCHARIDES project was fully successful in many areas, from fundamental research to applied development. This success of the project is mirrored on the one hand in a number of publications in high ranking international scientific journals, and more are currently being prepared for submission. On the other hand, the project also yielded a number of patents from different academic partners, and some of them are being used already by the commercial partners of the consortium.
Impact of the project
The NANOBIOSACCHARIDES consortium adopted, from the start, a pro-active approach towards the generation and further development of a viable plan for the use and dissemination of knowledge. For this purpose, one of the partners, a professional consultant with broad spectrum experience in the area of biopolymer applications, had the explicit responsibility to guide the scientists, throughout the whole duration of the project, towards realising the exploitable potential of their research results.
A logo and a corporate design were developed by a professional designer at the start of the project, leading to easy identification of the NANOBIOSACCHARIDES project, partners, results, and ideas. A PUDK seminar was organised to identify earlyon, the most promising areas for exploitable results, and responsibilities for these were distributed among the partners.
The project partners have identified a large number of exploitable results, some to be used inside and some outside the consortium. The most advanced exploitable results which are also already protected by patent applications have been selected for publication through the EU channels. These include a novel vector for the heterologous expression and secretion of eucaryotic proteins, a new generation of chitosan / cyclodextrin nanoparticles for protein and gene delivery, a new approach towards using chitosan as a novel type of MMP2 inhibitor to hinder the degradation of extracellular matrix and thereby the migration and invasion of e.g. cancer cells, and chitosan microemulsions as novel cosmetic delivery systems.
Throughout the project, and beyond, all partners have been and will be involved in diverse dissemination activities, both towards the scientific community, e.g. at national and international scientific meetings where some of the academic partners are regularly invited as key note speakers, and towards the general public, e.g. when the principal investigators are invited to schools or are inviting pupils to their labs, to discuss their work, their ideas, their results, and their visions.
The former will greatly be supported by the planned chitosan handbook and the interactive internet encyclopedia ChitoWiki which will be generated with the financial support and the scientific expertise of the NANOBIOSACCHARIDES project and consortium, respectively, and which was presented in September 2009 on the occasion of the 11th International Chitin and Chitosan Conference in Taipeh, Taiwan.
The NANOBIOSACCHARIDES project was based on the novel concept of biological decoys. A decoy is inspired by a natural material, but it does not simply copy it. A decoy resembles a natural structure partially, but it does not mimic it completely. Therefore, it may elicit only those aspects of a given natural reaction that are wanted, with no unwanted side reactions.
The NANOBIOSACCHARIDES project aimed at developing biological decoys based on naturally occurring polysaccharides. Polysaccharides, the most versatile and diverse class of biopolymers, have long been known to be information bearing molecules, but we lack a detailed molecular understanding of their biological activities. Their great complexity, diversity, and innate microheterogeneity make analysis and synthesis extremely demanding.
However, the emerging techniques of nanotechnology promise to allow analysis and manipulation at a molecular, nano-scale, and, possibly, single molecule level. The NANOBIOSACCHARIDES project has established cause-consequence links between the physico-chemical properties of polysaccharides, in particular of chitosans, in solution or as a nanosystem, and their biological activities.
Chitosan is an extremely versatile biopolymer with potential applications in the material and life sciences. However, the diverse life science applications - in fields such as medical biomaterials, drug and gene delivery, cell and tissue engineering, cosmeceutics, food technology, and agriculture - suffer from poor reproducibility of the effects observed.
The project partners have argued that this may at least partly be due to batch-to-batch differences in the insufficiently characterised chitosans commercially available today. The NANOBIOSACCHARIDES project focused on medical and pharmacological applications of nano-scale characterised chitosans as well as chitosan-based nanoparticles and physical hydrogels.
The chitosans, nanoparticles, and hydrogels were generated using advanced chemical and enzymatic procedures with known modes of action, yielding products with defined physico-chemical properties and biological activities. An in depth understanding of the structure-function relationships of biologically active polysaccharides will allow the development of nanoparticles made from decoy chitosans able to overcome biological barriers and to facilitate the delivery of complex drugs such as insulin via nasal, pulmonary, or oral routes instead of direct injection into the blood vessels.
Similarly, nano-structured physical hydrogels made from decoy chitosans will eventually allow to generate a suitable interface between biomaterial and living tissue, promising the generation of wound dressings under which the scar-free development of new skin tissue is induced. The NANOBIOSACCHARIDES project allowed an enlargement of the consortium by inclusion of selected international partners. This strengthened the aspect of enzymatic generation and analysis of chitosans with other than random patterns of acetylation with potential novel physico-chemical properties and biological functionalities. At the same time, the new partners also widenened the focus of the project to include other promising applications, such as in agricultural plant disease protection, and in skin-whitening cosmeceutics.
Not unexpectedly, the different areas of our project developed differently, some towards more basic research, some towards more applied development:
- One branch of the project took a more basic approach to understanding the physico-chemistry of polysaccharide solution properties and their involvement in spontaneous formation of nanoparticles, resulting in the formulation of a universal law of behaviour for polyelectrolyte polysaccharides in aqueous solutions. This now allows us to understand the continuum of polysaccharide solutions, nanoparticles, and physical hydrogels - and this will in the long run allow the development of reliable, knowledge-based applications.
- Another branch of the project took a more applied approach towards optimising the biological properties of polysaccharide nanoparticles by varying their compositions and mode of preparation, comparing their bio-compatibilities and their abilities to serve as drug, gene, or vaccine carriers for different types of human and animal cells. The results allowed us to identify the most promising types of nanoparticles for different potential applications.
The scope and reach of the NANOBIOSACCHARIDES project was widened to include cosmetics and agricultural applications, and both fields profited greatly from the fundamental and applied work done on nanoparticle formation and bio-compatibility so that further research strategies and potential avenues into markets were identified and defined.
Similarly, the work on enzymatic nanostructuring of polysaccharides, though it proved more difficult and time consuming than initially envisaged, finally led to proof of principle that the biological activities and potentially even the physico-chemical properties of polysaccharides are dependent on their nanostructure, namely on their patterns of substitution. This insight opened up a whole new area of research with enormous economic potential, mostly in the medical and food market sectors, which will be pursued in a follow-up European research project with strong industrial participation.
Overall, the NANOBIOSACCHARIDES project was fully successful in many areas, from fundamental research to applied development. This success of the project is mirrored on the one hand in a number of publications in high ranking international scientific journals, and more are currently being prepared for submission. On the other hand, the project also yielded a number of patents from different academic partners, and some of them are being used already by the commercial partners of the consortium.
Impact of the project
The NANOBIOSACCHARIDES consortium adopted, from the start, a pro-active approach towards the generation and further development of a viable plan for the use and dissemination of knowledge. For this purpose, one of the partners, a professional consultant with broad spectrum experience in the area of biopolymer applications, had the explicit responsibility to guide the scientists, throughout the whole duration of the project, towards realising the exploitable potential of their research results.
A logo and a corporate design were developed by a professional designer at the start of the project, leading to easy identification of the NANOBIOSACCHARIDES project, partners, results, and ideas. A PUDK seminar was organised to identify earlyon, the most promising areas for exploitable results, and responsibilities for these were distributed among the partners.
The project partners have identified a large number of exploitable results, some to be used inside and some outside the consortium. The most advanced exploitable results which are also already protected by patent applications have been selected for publication through the EU channels. These include a novel vector for the heterologous expression and secretion of eucaryotic proteins, a new generation of chitosan / cyclodextrin nanoparticles for protein and gene delivery, a new approach towards using chitosan as a novel type of MMP2 inhibitor to hinder the degradation of extracellular matrix and thereby the migration and invasion of e.g. cancer cells, and chitosan microemulsions as novel cosmetic delivery systems.
Throughout the project, and beyond, all partners have been and will be involved in diverse dissemination activities, both towards the scientific community, e.g. at national and international scientific meetings where some of the academic partners are regularly invited as key note speakers, and towards the general public, e.g. when the principal investigators are invited to schools or are inviting pupils to their labs, to discuss their work, their ideas, their results, and their visions.
The former will greatly be supported by the planned chitosan handbook and the interactive internet encyclopedia ChitoWiki which will be generated with the financial support and the scientific expertise of the NANOBIOSACCHARIDES project and consortium, respectively, and which was presented in September 2009 on the occasion of the 11th International Chitin and Chitosan Conference in Taipeh, Taiwan.
