SmartCubes · An innovative class of nanoparticles (“SmartCubes”) for the targeted delivery of protein therapeutics
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-06-01 → 2019-05-04
- EU contribution
- €185,857
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
An innovative class of nanoparticles (“SmartCubes”) for the targeted delivery of protein therapeutics
The objective of the ‘SmartCubes’ project was to develop a lipid nanoparticle that could be used to deliver protein therapeutics. Protein therapeutics offer exciting alternatives to common treatments as they are highly specific and commonly well tolerated. However, a significant challenge with protein therapeutics is how to package the protein to promote uptake and prevent rapid degradation before reaching the site of interest. Lipid nanoparticles offer a potential solution to this problem. Previous attempts to use similar lipid nanoparticles in protein therapeutics had reached a bottleneck due to limited pore sizes inside the nanoparticle and hence ability for loading larger proteins. This project demonstrated that it was possible to load large proteins into lipid nanoparticles and maintain their function. Novel pharmaceuticals are important for society to enable the continued development of medical treatments. Traditionally small drug molecules have been the cornerstone of treatment options, however scientific advances have led to new therapeutics such as protein therapeutics and therefore new challenges surrounding effective delivery. The overall goals of the project were to demonstrate that ‘SmartCubes’ could be used as a novel carriers of protein cargo for therapeutic delivery of large proteins. This was divided into two key areas; cargo loading and delivery to cell lines. The Karolinska Institute was an ideal location for this ambitious multidisciplinary project enabling me to apply my skills in fundamental nanoparticle science to biological applications. Working in a medically focused environment has enabled me to gain new insights into the challenges of developing novel therapeutics, build collaborations to develop the project and increase my skill set. The image attached to this report schematically demonstrates the intelligent design of cubosomes for biomedical applications and has been reproduced with permission from Barriga et al. Angew. Chem. Int. Ed. Engl. 2019 Mar 4, 58(10), 2958 - 2978.
Data: CORDIS, © European Union
Project objective
'SmartCubes' are an innovative class of nanoparticles for the targeted delivery of protein therapeutics. The objective is to deliver high levels of membrane proteins to cancer cells to combat disease. I will achieve this by creating novel 'sponge-like' targeted nanoparticles (SmartCubes) to selectively deliver unprecedented levels of a cancer therapeutic protein to colon adenocarcinoma cells.‘SmartCubes’ are based on a cubic membrane structure. They contain a highly stable lipid bilayer displaying a 'honeycomb-like' construction. This structure has prevented previous applications as the water channels were too small for large proteins to enter and reconstitute into the membrane. I am uniquely able to tune the sizes of the water channels within the 'SmartCubes' to create water networks sufficiently large to house a whole new class of proteins. I will achieve this new class of nanoparticles by creating 'SmartCubes', modifying the outer surface of the 'SmartCubes' with a selective antibody, loading the cubic membrane with a cancer therapeutic protein and delivering them to cancer cells.Protein therapeutics are an exciting alternative to conventional cancer treatments due to reduced side effects and their high target selectivity. I can surpass previous attempts which were limited by rapid protein degradation and the instability of the delivery vehicle. As protein therapeutics increase in complexity, there is a need for stable, high surface area, membrane based delivery systems. This project, hosted in the 2014 European life sciences group of the year, will transform my fundamental research into a platform technology that will revolutionise the field of protein therapeutics.
Original text from CORDIS.
Participants
- KAROLINSKA INSTITUTET · STOCKHOLMCoordinatorSweden
Links
Data: CORDIS, © European Union