Another paper accepted!

I also forgot to tell you that during the summer we got another paper accepted and published. The link for the paper is below:

L-type amino acid transporter 1 (LAT1)-utilizing efflux transporter inhibitors can improve the brain uptake and apoptosis-inducing effects of vinblastine in cancer cells

The study describes how chemotherapeutics can be delivered more effectively across the blood-brain barrier and into the cancer cells by co-treating them with a targeted efflux inhibitor that we have developed. The function of efflux pumps is one of the main mechanisms for chemoresistance and also the prevention of drugs accumulating into the brain. Efflux pump inhibitors have been developed for decades to improve anti-cancer therapy, but unfortunately, with lack of success, since efflux pumps have also a crucial role in healthy cells. Therefore, in our attempt, we created a prodrug of an efflux pump inhibitor that was able to utilize a familiar transporter, LAT1 (L-type amino acid transporter 1), which is over-expressed in many different types of cancer. Thus, in our study, the LAT1-utilizing derivative of probenecid was able to increase the brain uptake of another anti-cancer drug, vinblastine, and consequently its accumulation into the cancer cells, which in turn improved the apoptosis-inducing effects of vinblastine. Moreover, the LAT1-utilizing derivative of the efflux pump inhibitor was found to be hemocompatible, meaning that it is safe in the systemic circulation. This study was a continuation of our previous study:

Targeted efflux transporter inhibitors - A solution to improve poor cellular accumulation of anti-cancer agents 

and the present study was carried out in a collaboration with Dr. Magdalena Markowicz-Piasecka from the Medical Univerisity of Lodz. So thanks for all who contributed to this study and the one preceding it!

Back to School

The summer holidays are mainly over in Finland and the school, as well as the semester at the Universities, have already started. I had a relaxing summer break, however, the scientists never have a real break, which is sometimes difficult fo non-scientists (like my husband) to understand. But this summer was not that bad, only a few manuscript readings, galley proof checkings and "some emails and phone calls" :). 

We luckily get one of the very challenging and long-lasting projects published in Molecular Neurobiology. The studied under the title

"Targeting of Perforin Inhibitor into the Brain Parenchyma Via a Prodrug Approach Can Decrease Oxidative Stress and Neuroinflammation and Improve Cell Survival" (link to the publication)

describes how a prodrug that utilizes LAT1 transporter and is delivered more effectively into the brain (across the blood-brain barrier) and into the brain parenchymal cells (e.g., neurons, microglia, and astrocytes) can improve its pharmacological effects. The parent drug of this prodrug is a perforin inhibitor (molecules that I worked with at the Auckland Cancer Society Research Centre in New Zealand 2009-2011) and it is supposed to inhibit endogenous perforin protein that is released e.g., in neurodegenerative diseases and which aids in destroying brain cells. Moreover, with LAT1-utilizing prodrug we were able to affect several different factors related to inflammation and oxidative stress in the brain (which is also associated with several neurodegenerative diseases) and to our surprise, the compound also inhibited an enzyme function, very special hallmark to Alzheimer's disease (BACE1; β-site amyloid precursor protein (APP) cleaving enzyme 1) and thus, our prodrug was functioning as a multitargeted drug within the brain. Most importantly, this publication is one of the first ones to show that rationally developed LAT1-utilizing prodrugs of a selected parent drug can really result in improved brain drug delivery and subsequently improved pharmacological effects! 

Thanks for the team for the great effort! :)

Summer Break

Most of the Finnish scientists have already started their summer break, July is always a very quiet time at the Uni. Although sometimes it feels it is impossible to have a break from the research, a distance to your work does always good. It refreshes your thoughts for sure! I have been working mainly at home until today, and for me, the last 4 weeks have been even tougher than the exact COVID-19 isolation, since then the kids had something to do, unlike now...! Due to the lack of different group activities this summer, the days have been filled with a lot of electronic content, unfortunately. Luckily, we spotted a science camp organized by our science center "Heureka" (located in Helsinki; www.heureka.fi) that was held via zoom and all we had to do was to buy a lot of citric acid and baking soda! 😄 And a little bit other ingredients... and of course to clean up the mess after every day... 😂 But this was a really good experience for both me and 7-years' old and I think his interest towards natural sciences increased and afterall he had fun every day, even afterwards when doing extra experiments by himself. So thanks Heureka, job well done!

Now, I will take a break too, see you in August! 

Have nice, sunny, and relaxing summer!