H2020Individual fellowship2017–2019

GlycoNanoPep · Glyco and Nano Peptide Conjugates for Selective Cell Penetration

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2017-04-01 → 2019-03-31
EU contribution
€158,122
Participants
1
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

Glyco and Nano Peptide Conjugates for Selective Cell Penetration

Recent advances in genomic technologies have made possible the identification of new therapeutic targets that could be addressed with a variety of drugs (small molecules, proteins) or gene therapies (DNA, siRNA, CRISPR). Although this wide range of potential drugs is available, their use is however hampered by the intrinsic difficulty in the delivery of drug and genes into the cells of interest. In addition, further difficulties arise from the interaction of the cargos (i.e. nucleotides) with the diverse components of the biological media, which includes the presence of nucleases, proteases and other dissolved proteins. Therefore, the design of innovative delivery systems that can protect the drug and improve their selective and efficient biodistribution in a complex biological media constitutes a critical stepping-stone towards the development of new nanomedicines or imaging strategies. The goal of this project is the development of dynamic multivalent glycoconjugated cell penetrating peptides (DyGCPPs) and nanoparticles (GNP-DyCPPs) as a powerful tool for selective membrane permeation of active components at a cellular level. This might serve for the development of new therapeutic strategies that prevent side effects of the conventional biodistribution cell penetrating peptides (CPP): allow specific delivery of CPP to specific tissues and prevent degradation of CPPs by interaction with biological components (serum, proteins, etc.). The work developed in this proposal has allowed the control over the formation of supramolecular nanoparticles constituted by multiple elements and their intracellular delivery using penetrating peptide vehicles. These results will open new directions for conceptually new artificial drug delivery systems. This new knowledge will benefit the progress in key enabling technologies for the future social challenges in health and biomedicine.

Data: CORDIS, © European Union

Project objective

The next generation therapeutic agents such as proteins, nucleotides, cytotoxic agents and molecular probes hold promising properties to solve many crucial health issues. However, efficient and selective transport of this therapeutic cargos and imaging probes into the right cells at the right moment stands as a fundamental limitation of these new technologies.In this action we will develop a new generation of highly efficient, selective and biocompatible supramolecular vehicles for specific cell delivery. This strategy will consist in the implementation of dynamic bonds as linkers for glycoconjugated cell penetrating peptides. These peptide hybrids will be recognized very specifically carbohydrate receptors and internalized. These stimuli responsive dynamic bonds will assist in critical steps of the delivery process such as the cargo release and endosomal escape.We will expand this strategy to incorporate glycopeptides conjugated into multifunctional nanoparticles through host-guest interactions. We will implement state of the art synthetic, biophysics and cell biology techniques to identify new supramolecular selective membrane transporters.This action will combine the glycochemistry background of the applicant with the expertise in membrane transport of the host group. The potential discoveries will trigger new opportunities in the delivery of the next-generation probes and proteins (i.e. CRISPR).

Original text from CORDIS.

Participants

  • UNIVERSIDAD DE SANTIAGO DE COMPOSTELA · Santiago De CompostelaCoordinatorSpain

Links

Data: CORDIS, © European Union