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Dynamic bonds and polyion complex (PIC) nanoparticles for targeted intracellular peptide delivery

Project description

Peptide delivery through hybrid nanoparticles

Various peptide-based biologics are being developed, but their poor intracellular delivery impedes their widespread application. The EU-funded DynaPIC project will develop a strategy for protecting these peptides and ensuring their efficient delivery within cells. Researchers will employ dynamic covalent bonds to produce hybrid peptide–polymer nanoparticles with cell-targeting and permeation properties. Functionalisation with specific surface ligands will ensure specificity, while cellular uptake of these nanoparticles will trigger their disassembly and cargo release inside the cells. These hybrid peptide nanoparticles can be utilised as antimicrobial agents to kill pathogens inside infected cells.

Objective

The therapeutic action of many peptides is limited by their poor stability in biological media and lack of cell specificity. In particular, cationic peptide amphiphiles are promising antimicrobial tools, but their targeted delivery inside infected host cells to kill intracellular pathogens remains challenging. Our goal is to develop a new supramolecular strategy to protect these peptides and provide them with cell specificity towards their safe and efficient intracellular delivery.

In this project, we will combine dynamic covalent bonds, supramolecular, peptide and polymer chemistry, together with chemical biology, to develop a conceptually new targeted drug delivery platform: Hybrid polymer/peptide self-assembled nanoparticles combining stimuli-responsive, cell-penetrating and cell-targeting properties will be applied to the intracellular delivery of cationic peptide amphiphiles inside infected cells.

We will prepare combinatorial libraries of cationic peptide amphiphiles that will be screened for membrane permeation and antimicrobial activity to find suitable dual-action peptides for intracellular application. These amphiphilic peptides will be self-assembled with anionic stimuli-responsive polymers into organic nanoparticles designed to disassemble and release their cargo upon cellular uptake, in response to pH reduction in the endosome. Under these conditions, the dynamic bonds present in the peptide amphiphiles can be broken to release conjugated molecules of interest (e.g. drugs, fluorescent probes, etc.). Cell targeting will be achieved by controlling nanoparticle size and by decorating the polymers with ligands for specific recognition by cellular receptors. Dual-action peptides will diffuse across cellular compartments to attack pathogens in the cytosol. The biological activity of peptides and nanoparticles will be assessed with advanced chemical biology and imaging techniques in suitable biological models.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 160 932,48
Address
COLEXIO DE SAN XEROME PRAZA DO OBRADOIRO S/N
15782 Santiago De Compostela
Spain

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Region
Noroeste Galicia A Coruña
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 160 932,48
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