STOPP Vehicles · Specific Targeting of Organelles using Peptide-Polymer Vehicles
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2013-03-01 → 2015-02-28
- Финансиране от ЕС
- 184 709 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Пептидно-полимерни носители се тестват за доставка на лекарства до специфични части от клетката, като например ендоплазматичния ретикулум. Това помага да се разбере как да се заобиколят процесите по разграждане в клетката, за да достигнат терапевтичните вещества до целта си.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Specific Targeting of Organelles using Peptide-Polymer Vehicles
Controlling the intracellular uptake of macromolecular therapeutics is of great interest for the development of novel drug delivery carriers. Favouring internalization via caveolae-mediated endocytosis, for example, would allow by-passing of the degradative pathway and increased delivery of the cargo in the endoplasmic reticulum (ER) and Golgi apparatus (GA) of cells. One strategy would be to mimic the activity of bacterial toxins derived from Escherichia coli (ET) and cholera toxin (CT) which, upon binding to ganglioside GM1 receptors found on the cell surface, internalize via caveolae-mediated endocytosis and travel to the ER of cells via the retrograde pathway. A number of small peptide sequences that binds to these GM1 receptors has already been identified. Unfortunately, no in-depth study of the intracellular uptake and trafficking of these sequences has been carried out so far. In this study, three of the most promising GM1-binding sequences from the literature: VWRLLAPPFSNRLLP, NPPSPLSVSHRT, and HLNILSTLWKYR were synthetized, modified with a cysteine for ease of functionalization, and systematically studied for their cytotoxicity, affinity towards GM1 receptors, uptake pathway and intracellular trafficking. Results showed that these peptides were internalized mostly via a combination of clathrin-mediated endocytosis and macropinocytosis, leading to their accumulation in the lysosomes of cells. The potential of these peptides to be used as drug delivery carrier was also investigated using an assay based on the cross-presentation of a model antigen to dendritic cells. Whereas no significant enhancement of the antigen presentation was observed, useful conclusions could be drawn regarding the use of GM1-binding moieties for antigen delivery purposes. This discovery is of great importance for the future development of novel antigen carrier and will need to be taken into account in the wider effort to develop novel forms of vaccination worldwide.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
In the past ten years, research in the area of drug delivery has focused on the development of vehicles that can target specific cells in the body and on the development of vehicles that specifically deliver a drug within these cells. Today, science is going one step further and the creation of vehicles that can target specific organelles within the cell is the new challenge. In this project, I aim at creating a new generation of peptide-polymer conjugates that can specifically target the Endoplasmic Reticulum (ER) and/or the Golgi Apparatus (GA) of cells. A direct application for such vehicles is the possibility to deliver antigens into dendritic cells directly in the place where they can bind to the MHC Class I complex. Efficient delivery of antigens to the MHC Class I complex triggers the activation of CD8+ cytotoxic T lymphocytes and is crucial for the creation of novel and more efficient vaccines and adjuvants. The use of polymers for targeted antigen delivery would have many advantages, not the least being an enhanced plasma half-life of the drug, improved solubility and the possibility of controlled release. The success of this will lead to the creation of a novel generation of polymeric-based immunogenics.
Оригинален текст от CORDIS (на английски).
Участници
- ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE · LausanneКоординаторШвейцария
Връзки
Данни: CORDIS, © Европейски съюз