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Light triggered non-invasive gene delivery through lipopolyplexes

Periodic Reporting for period 1 - LIGHTOPLEX (Light triggered non-invasive gene delivery through lipopolyplexes)

Reporting period: 2018-09-01 to 2020-08-31

Biomedical research and development rely on powerful test systems. In the past, test systems that address cellular processes made use of cell cultures in Petri dishes at one end and test animals at the other end. Both approaches suffer from limitations that have severely hampered progress in medicine, in pharmacology and toxicology in recent years. Presently, there are enormous efforts to establish novel physiologically relevant cell models that accurately mimic human tissue and organs in order to provide systems for the study of disease, for drug screening and for the assessment of the toxicity of compounds. The benefit of these cell models strongly depends on the tools for controlling cellular parameters and for manipulating cellular behaviour. In this project, a novel tool for the delivery of bioactive compounds into cells has been developed.
The novelty of this approach lies in the employment of inorganic particles from the mineral, vaterite calcium carbonate. These particles feature an enormous loading capacity for bioactive molecules due to their porous structure, fully biocompatible encapsulation approaches, and have the ability to entirely dissolve within cells and deliver their cargo in a controlled manner. In this project, these particles have been investigated as vectors for encapsulation, protection, and triggered release of bioactives of a various nature from small anticancer drugs and up to large and fragile biomacromolecules such as proteins and enzymes. It has been demonstrated that the particles can be internalised into cells together with a substantial molecular load. Internalisation has been facilitated by coating the particles with polymers. Based on previous work and on the achievements accomplished in this project, now, a solid foundation is laid for further investigation that should focus on quantitative aspects such as transfection efficiency and load that can be deposited in the cells. The results of the project are disseminated via publication in peer reviewed journals and presentation at scientific conferences and meetings. The results of this project are available for public increasing a chance of interest from industry and relevant stakeholders.
The establishment of cell models of high physiological relevance and of powerful tools for their manipulation has enormous impact in fields such as toxicology, drug and vaccine development as well as biomedicine. Progress in all of these fields is vital to the wellbeing of European citizens. It strongly depends on the development of robust and convincing technological solutions for the exploitation of relevant cell models. In this project a highly innovative approach for the introduction of biomolecules into cells was explored. The attractivity of the fully degradable and biocompatible delivery vectors from vaterite for industry is high because of the ease of production of these particles and their cost effectivity. This work stimulates to further develop and employ for bioapplications not only vaterite particles as drug delivery vectors but also other very promising naturally derived nano- and micrometre-sized particles such as halloysites and nanocellulose as per the schematics below.
Naturally Derived Nano- and Micro-sized Vehicles for Bioapplications