Welcome to the Nanomedicine homepage, which features news and information about the different projects in the research group led by Lars Herfindal.
Repurposing, or redefinition of drugs from one disease to another, is a way to improve treatment of diseases with few therapy options. For acute myeloid leukaemia, the anti-psychotic drug chlorpromazine has showed good effect in cell cultures in vitro. However, it has quite dramatic effects on the central nervous system in non-psychotic individuals. PhD student Edvin Tang Gundersen has developed a nanoparticle which encapsulates chlorpromazine, and prevents it from entering the central nervous system. The formulation is efficient towards AML cells and the nanoparticles prevent the encapsulated molecules crossing from the blood into the central nervous system in zebrafish larvae. The work was recently published in International Journal of Pharmaceutics.
Together with Hanne R Hagland and Abdelnour Alhourani at the University of Stavanger, we have investigated if graphene nanosheets can be used to transport small anti-cancer drugs in the blood. Graphene nanosheets have unique properties that are not found in other nanomaterials, such as a very high surface area for absorption of drugs. We found that graphene released the drugs at low pH, which are perfect for cancer drugs, since most tumours have lower pH than the rest of the body. We also demonstrated that pristine graphene is superor to graphene oxide, but that PEGylation is needed to ensure that the nanosheets disperse nicely in aqueous media. The work was just accepted for publication in ACS Omega.
Many years ago, we came across an interesting compound, iodinin, from marine benthic bacteria, which selectively induced apoptosis in leukaemia cells. In fact, the compound was first described more than 70 years ago, but has not been left much attention. We also almost put it aside, until our good collaborators Pål Rongved and Elvar Örn Viktorsson managed to develop a method to synthesise iodinin in the lab, and even better, produce variants which could be even better as drugs. We recently got our work accepted for publication in RCS medicinal chemistry. Here, Pål and Elvar has produced more than 60 analogues of iodinin, which we tested for ability to kill leukaemia cells. The results can tell us something about which parts of the molecules are crucial for the activity, and which part can be improved so we get even better activity, and milder side-effects.
Inside our blood, there are several natural nanocarriers. Lipoproteins are small packages of lipids, stabilised by proteins. These transport lipids and some lipid-soluble vitamins in the blood, and deliver them at the target sites. We have found that some lipid-soluble drugs also associate with lipoproteins, and a large fraction of these are transported by lipoproteins rather than serum proteins. This new concept of drug transport in the blood means that we have to think differently when estimating pharmacokinetic properties of some drugs. The paper was published in the journal Therapeutic Drug Monitoring.
Although immune-based therapies emerge as promising to fight cancers, we will still rely on small molecules for most of the patients. Together with researchers at Clermont-Ferrand, we have investigated inhibitors of Pim-kinases to kill acute myeloid leukaemia cells. Of the molecules we tested, one was particularly promising, and proved efficient also towards leukaemia cells isolated from patients that had developed chemotherapy resistance. Why was our molecule so efficient? Probably because in addition to blocking Pim-kinase activity, it also inhibited other key signalling factors in the leukaemia cells. The work was recently published in Molecular Cancer Therapies.
The figure shows the different molecules tested, and VS-II-173 stands out being very efficient towards acute myeloid leukaemia (AML) cells, and not towards non-malignant cells. Green indicates low toxicity, red indicates high toxicity.
Can nanocarriers improve therapy for children with cancer? This is something we want to find out, and we recently received a grant from the Norwegian Children’s Cancer Society to investigate this. This is part of a large project, led by specialist in pediatric cancer Maria Winther Gunnes, and with Camilla Tøndel, Randi Hovland, and Emmet McCormack as project participants. Together, we hope to improved the treatment of cancer in children.
Just after Christmas, we got the nice news that our manuscript on tyrosine hydroxylase (TH) in nanoparticles was accepted for publication in Bioconjugate Chemistry. This work describes an amitious, but very elegant principle for treatment of neurodegenerative diseases like Parkinson’s disease. In this disease, the patients suffer from loss of enzyme activity. We showed that it was possible to load functional enzymes into nanoparticles. The nanoparticles internalize the functional enzymes both in cells in culture, and in animals. The work was mainly done by Maite and Fredrik in Aurora Martinez’ group, but also with contributions from Edvin and myself.
This year, we decided to join most other cancer researchers in Bergen to the CCBIO annual symposium at Solstrand hotel. Sarah and Ronja presented a poster on their findings on how the cAMP receptors Epac1 and PKA influences the pressure inside tumours, and subsequently nanoparticle accumulation. This was part of Sarah’s master thesis, and Ronja has supplied excellent data on tumour pressure measurement. A poster is the first presentation of data, and has given us an idea of how the final article will be. We will now start to gather together a manuscript.
Here are the two happy scientists in front of the poster presenting their research.
We finished 2016 with a Christmas Lunch. Even though 2016 was nice, we are sure that 2017 will be even better. Edvin and Sarah will join as PhD students. Edvin got a grant from “Helse-Vest”, and Sarah will start in a UiB-funded PhD grant. Jan-Lukas will start his masters thesis on graphene, which is joint with the University of Stavanger (Hanne Hagland) and Cealtech.
We will shortly move to a new cell culture lab, with new equipment, and the system for zebrafish injection will arrive within a few weeks, so things look bright. We are now quite a few people working with nanomedicine, so the new equipment will come in handy from the very start.
Below you can see a happy bunch of scientists looking forward to next years experiments. Ronja behind the camera.
Gard and Kenny were in our lab doing their project as part of the introductory course in nanotechnology (NANO100). They took part in production of nanoparticles directed towards acute myeloid leukaemia, experiencing both success and failure in the lab. Their final task was to make a poster on their work and results in the lab. The poster was awarded best poster among all the NANO100 students. Below is a picture of the two proud nanoscientists with their poster and diplomas.