Blogger: Sjoerd Hak
The Research Council of Norway has recently awarded grants under the funding scheme Independent Basic Research Projects – Medicine, Health Sciences and Biology (FRIMEDBIO). There is tough competition for this funding nationally, and only the best projects get through. The Faculty of Medicine, NTNU, has been awarded funding for three talented young researchers, three research projects and two post docs. You can read about all these projects on the blog over the coming weeks. Sjoerd Hak received FRIMEDBIO-funding for his post doc project: “Multimodal in vivo study of nanoparticle decomposition and targeting dynamics”
In the field of nanomedicine, the use of drug loaded nanoparticles to deliver drugs to tumours is now well established (see Figure 1).
Tumour bloodvessels are very leaky as compared to healthy vasculature. When drug loaded nanoparticles are injected into the bloodstream, they can leak from the leaky tumour bloodvessels into the tumour tissue; whereas leakage from the blood vessels in healthy tissue is limited.
Exciting developments in nanotechnology have allowed for the production of a wide variety of advanced nanoparticles.
As compared to conventional therapy without nanoparticles, this results in a larger part of the injected drugs ending up in the tumour and a reduction in side effects (Figure 1B).
Figure 1. A: General design of a nanoparticle loaded with drug. The core/shell/surface coating can be composed of a variety of different materials, which has resulted in an enormous diversity in the design, and hence properties, of different nanoparticles. B: When a drug loaded nanoparticle is injected into the blood, it can leak into the tumour tissue due to the leaky tumour blood vessels. C: General design of a targeted nanoparticle loaded with drug. D: Nanoparticles can be specifically targeted to the cells making up the tumour vasculature. When these are injected into the blood, they accumulate in the tumour vasculature. The targeting and subsequent disrupting of tumour blood vessels is a promising therapeutic strategy. E: Nanoparticles can also be specifically targeted to cancer cells. When these targeted nanoparticles are injected into the blood, they accumulate in the tumour and bind to tumour cells, increasing the amount of drug delivered to individual cancer cells.
Although this has improved therapy for a group of cancer patients, the full potential of nanoparticles in cancer therapy remains to be explored. Exciting developments in nanotechnology have allowed for the production of a wide variety of advanced nanoparticles.
One highly interesting development is the synthesis of so-called targeted nanoparticles: Nanoparticles equipped with molecules on their surface making them specifically recognise and accumulate in tumour tissue (Figure 1C). This is a very promising approach to deliver drugs specifically to tumours and to spare healthy tissue (Figure 1 D-E).
For the development and successful application of such targeted nanoparticles, detailed studies to learn about and understand the in vivo behaviour of these novel targeted nanoparticles are essential.
For example, it is not well known how fast targeted nanoparticles accumulate in tumour tissue after injection. Moreover, it is now becoming clear that certain nanoparticles readily disintegrate upon injection into the blood, resulting in drug release in the blood. As such, the drug may be released before the tumour is reached. Hence, knowledge of nanoparticle degradation and tumour targeting rates and dynamics are crucial for successful development and application of targeted nanoparticles. However, these dynamics remain largely unstudied, which may be compounded by the fact that suitable experimental in vivo tools to do so are lacking
Ultimately, we anticipate to fine-tune our nanoparticle design and increase their value in the battle against cancer.
Over the last four years, during my recently completed PhD project, we have established the synthesis of innovative nanoparticles of which such dynamics can be quantitatively monitored. Furthermore, combining in vivo microscopy and magnetic resonance imaging, we have developed a unique experimental set-up which is highly suitable to study in vivo nanoparticle dynamics.
Over the next years, this novel experimental approach will be exploited to study degradation and targeting dynamics of our nanoparticles at an unprecedented level of detail. Importantly, this will provide general knowledge applicable to a variety of targeted therapies. Ultimately, we anticipate to fine-tune our nanoparticle design and increase their value in the battle against cancer.