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NANO2021-Nanoteknologi og nye materiale

Engineered nano-based device for glioblastoma multiforme therapy (Nano4Glio)

Alternative title: Engineered nano-based device for glioblastoma multiforme therapy (Nano4Glio)

Awarded: NOK 5.0 mill.

Nano4Glio is a transnational European project with partners from Portugal (coordinator), Denmark and Norway. The consortium is comprised of experts within design and development of nanocarriers and characterization of nanomedicines, as well as pharmacists and cell biologists. The main goal of the project is to develop new forms of treatment for glioblastoma multiforme (GBM). GBM is a severe form of brain cancer with high mortality, and both the disease and the existing treatments have severe detrimental effects for the patient. In Nano4Glio, we will develop a new type of treatment wherein the drug is encapsulated within nanoparticles which are slowly released from an injectable gel. This allows for continuous treatment of the patient, thus reducing the need for travelling to a hospital for infusion, which currently is the most common drug administration route. The project has two major challenges to overcome. The first is to design a gel where the nanoparticles are stable over a prolonged period of time, but which degrades and releases the drug when the nanoparticles are transported out of the gel and into the tumour. The second challenge applies to all forms of treatment of diseases in the brain – crossing the blood-brain barrier. The blood-brain barrier protects the brain against foreign substances and helps maintain an optimal physiological environment in the brain. When delivering a medical substance/drug to the brain this becomes a problem, as the drugs we want to deliver are not allowed access across the blood-brain barrier and into the brain. Thus, we have opted for a strategy where the drug-containing nanoparticles should allow for recognition and passage by the blood-brain barrier, allowing for delivery of the drug to the brain tissue. The tasks of the Norwegian partner are the design and development of biodegradable, nanoparticle-loaded hydrogels, that easily can be injected subcutaneously and are suited as a depot for nanoparticles for at least 6 weeks. The Norwegian partner will also contribute with preclinical characterisation of both drug-loaded nanoparticles and the nanoparticle-loaded hydrogel, both physico-chemical characterisation, as well as in vitro cell-based safety and efficacy studies. During the first year, focus has been on the development of suitable biodegradable hydrogels, by screening several synthetic and natural polymers. Both empty and nanoparticle-loaded gels have been carefully characterized. Initial promising candidates with suitable mechanical properties have been achieved and dye-loaded model nanoparticles from the Portuguese partner have been incorporated to optimize the amount of nanoparticles and the incorporation process and to study release of the nanoparticles and the dye. Also, preclinical characterisation of drug-loaded nanoparticles from the Portuguese partner have started. The project had a kick-off meeting late in 2022 and a face-to-face project meeting in September 2023, where the partners discussed the first achieved results and made plans for the next year. The partners also had a meeting with the external advisory board, among other also clinicians, that gave important input for a future successful translation to the clinic.

Nano4Glio er et transnasjonalt Europeisk prosjekt med partnere fra Portugal (koordinator), Danmark og Norge. Konsortiet består av eksperter innen fremstilling av nanobærerutvikling, karakterisering av nanomedisiner, farmasøyter og cellebiologer. Hovedmålet med prosjektet er å utvikle nye behandlingsmetoder for glioblastoma mulitforme (GBM). GBM er en svært allvorlig hjernekreft med høy dødelighet, og både sykdommen og eksisterende behandlingsformer har stor negativ effekt på pasienten. I Nano4Glio skal vi utvikle en ny type behandling hvor legemidlet kapsles inn i nanopartikler som frigis langsomt fra en injiserbar hydrogel. Dette muliggjør en kontinuerlig behandling av pasienten og reduserer behovet for å oppsøke sykehus for infusjon som er den vanlige typen av administrering. Prosjektet har to store utfordringer å løse. Den første er å lage en hydrogel hvor partiklene er stabile over lang tid, men som brytes ned og leverer legemidlet når de transporteres ut av gelen og inn i tumor. Den andre utfordringen er gyldig for all behandling av sykdommer i hjernen, og er koblet til det som kalles blod-hjerne barrieren. Blod-hjerne barrieren beskytter hjernen mot fremmede stoffer og ser til at miljøet i hjernen alltid er optimalt. Når vi skal levere legemiddel til hjernen blir dette et problem, siden legemidlene vi ønsker å levere ikke kommer inn i hjernen. Vi har derfor valgt en strategi hvor nanopartiklene som innholder legemiddlet skal kunne gjenkjennes av blod-hjerne barrieren og dermed tas opp i hjernen.

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NANO2021-Nanoteknologi og nye materiale