A new study by scientists led by Oleg Lunov of the Division of Optics of the Institute of Physics of the Czech Academy of Sciences sheds light on how a cell's shape and mechanics influence its absorption of drug carriers. This research could lead to innovative targeted therapies, particularly in cancer treatment, where nanostructures could deliver drugs directly to cancer cells. The experiments have been carried out on liver cancer cell lines. The results were published in the prestigious Journal of Materials Chemistry B.
Targeted drug delivery getting drugs precisely into cells is a hot area of research. One promising approach uses DNA nanostructures (DNs) based on DNA nucleotides, the basic building blocks of genetic information. These nanostructures have unique properties such as easy programmability, synthesis and low toxicity. However, to really use their potential, we need to understand how cells interact with and take them up.
"Previous research mainly focused on the physicochemical properties of DNs – their shape, size or surface finish. However, our study shows that a key role in this process is played by the mechanics and shape of the cells themselves.
Cell shape influences the uptake of nanostructures
Imagine cells as flexible building blocks that adapt to their surroundings. When placed on specially shaped surfaces, like circles or narrow strips, they change their shape to fit. This shape change affects not only their outward appearance but also their internal structure, the cytoskeleton, made of protein fibers like actin. Cells in the center of circles tend to be rounder with less developed actin filaments, while at the edges these filaments become much stronger and generate greater mechanical forces. Cells growing in strips stretch in one direction and their actin filaments align perfectly along the axis of the strip.
This natural "rearrangement" of cells is key to how they absorb DNA nanostructures through a process called endocytosis. The tighter and more organized cell’s actin filaments, the more efficient it is in DNs uptake. This explains why cells at the edges of circles or narrow strips, with better organised actin cytoskeleton, absorb DNs more efficiently than cells in the center of circles. Experiments using a substance (inhibitor latrunculin A) that blocks actin formation confirmed this: when actin was disrupted, the cells' ability to absorb DNs almost disappeared, showing how important the forces generated by the actin cytoskeleton are.
"The results are a great example of an innovative approach and precise experimental work. If this principle can be applied clinically, DNA nanostructures could serve not only as drug carriers but also as tools for various biomedical applications," said Alexandr Dejneka, Head of the Division of Optics.
New possibilities in targeted therapy
Due to the different mechanical properties of cells, DNA nanostructures can be designed for targeted delivery to cells with specific morphologies. This could have a huge impact, for example, in the treatment of cancer, since cancer cells often differ from healthy cells not only genetically but also mechanically.
For more on the issue of DNA nanostructures, see this text for a summary of our knowledge in this area and this text for a summary of our knowledge in this area and this text on influencing the function of lysosomes in cells using a DNA nanostructure-based platform.