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NANO2021-Nanoteknologi og nye materiale

Assembling against Resistance: Antimicrobial Nanoparticles based on Molecular Assembly

Alternativ tittel: Samlet mot Resistens: Antimikrobielle nanopartikler gjennom molekylær selv-organisering

Tildelt: kr 9,2 mill.

Prosjektleder:

Prosjektnummer:

315666

Søknadstype:

Prosjektperiode:

2021 - 2024

Samarbeidsland:

Utbredelsen av antibiotikaresistens blant sykdomsfremmende bakterier er en av de største utfordringene innenfor global helse i årene fremover. Antimikrobielle peptider har lenge vært fremmet som et bedre alternativ til dagens antibiotika ved at den virker på den generelle cellemembranen til bakteriene uten å generere særlig resistens. En av de store problemene med disse stoffene er midlertidig at de vil brytes ned i kroppen og også kan gi visse bivirkninger og toksisitet. I dette prosjektet, ANTISOFT, skal vi jobbe med å utvikle nanopartikler som kan innkapsle og beskytte disse stoffene slik at de brukes mot patogene bakterier. I prosjektet vil vi finne nye strategier for å designe effektive nanopartikler og systematisk teste aktivitet mot bakterier samt potensiell toksisitet mot celler.

Antimicrobial peptides (AMPs) are found in many species throughout nature to fight pathogens such as bacteria or even by bacteria themselves to fight other bacteria. Human saliva and sweat contains AMPs as a part of the innate immune system to fight infections. Some AMPs act against fungi, viruses and even tumors. These molecules have been around for hundreds of millions of years and have largely been able to avoid bacterial resistance. Yet, they are surprisingly little used in treatments – mainly because they are rather unstable towards serum proteins and may be toxic to other cells. Here we will focus on the use of peptides assemblies as a modular antimicrobial system with tunable interactions and release profiles. By understanding their self-assembly and lipid interactions, we will create a toolbox for nanostructured AMPs, i.e. ” soft matter antibiotics”. In order to utilize these compounds, research is needed in order to understand how they work and how they need to be modified to enhance stability and reduce toxicity. In this project we have gathered a multi-disciplinary team to address these challenges. By combining experts within fields of synthetic chemistry, scattering techniques and computer simulations with experts within biochemistry and molecular biology, we will create antimicrobial nanoparticles, i.e. AMP assemblies with significantly reduced toxicity and enhanced stability. We will synthesize new materials, study the assemblies in solution and near lipid model membranes in order to get insight into their mechanism of action, and we will determine the resulting stability towards proteases. Selected promising compounds will be compared towards biological function, their antimicrobial activity and toxicity towards organs using a ”organ-on-chip” approaches. From this insight, we will facilitate the design of new materials that can be used for therapeutic against growing threats of multi-resistant strains of bacteria.

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NANO2021-Nanoteknologi og nye materiale