Micromotors, caregivers at the heart of our cells

Thousands of microscopic robots that are activated in our intestines, our veins, our organs, to come to treat, remove or repair: one would think of a science fiction scenario. Yet the dream of such non-invasive medicine may be coming true.

More and more micromotors, particles of the order of ten micrometers, capable of evolving autonomously and of responding to stimuli from their environment by changing their shape or activity, are being developed and tested in laboratory. These microswimmers made of biocompatible and biodegradable materials exist in many forms. They can travel through the human body to their target (a tumor or a thrombosis, for example), where their function is activated by an external signal or by an intrinsic change in physico-chemical conditions. Enough to deliver drug molecules or cells directly to the desired location, perform microsurgery or microbiopsies, detoxify or unblock thrombosis. All with processes that are neither toxic nor invasive.

These micromotors can be administered intravenously or orally, encapsulated in capsules and released into the intestine, where they can target lesions. For the moment, it is the oral route that is the most tested in the laboratory, although the venous route allows access to a greater number of organs.

Injection of micromotors

These micromotors can be administered by venous route or by orallythe latter being for the moment the most tested in the laboratory.

Remote control

The micromotors are controlled by lasers NIR (infrared).

Propulsion by autothermophoresis

Gold is able to convert the infrared energy it receives into heat. Since the metal covers only one side of the ball, the heat irradiation is asymmetrical, creating a temperature gradient. The water molecules will move faster on the hot side than on the cold side.
This causes an imbalance of forces around the particle which induces its propulsion.

endocytosis

Guided to the tumour, these micromotors pass the biological barriers to the membrane of the cell which absorbs them.

Integration into lysosomes

Lysosomes are pockets in which cells internalize everything that comes from outside. Their very acidic pH makes it possible to treat, or even degrade, foreign bodies.

Degradation

The acid pH of the lysosome will activate the dissolution reaction of the calcium carbonate particle producing microbubbles of CO₂.

Propulsion out of the lysosome

Thanks to the directed jet of microbubbles, the micromotor will come out of the lysosome.

drug release

The dissolution of the calcium carbonate particles also allows the release of the doxorubicin molecule.

cell death

Doxorubicin enters the nucleus and will attack the DNA, which will cause cell death. This is why it is important to specifically target cancer cells.

Infographics : The worldEva Desvigne Hansch and Audrey Lagadec

Sources : Xiang Zhou et al., J. Chem. Eng.2021
Huaijuan Zhou et al., Cyborg and bionic systems2022

To follow these microswimmers in the body, various medical imaging techniques can be used. Photoacoustic tomography, which has previously been used in micromotor tracking experiments in the gut of live mice, is a non-invasive hybrid imaging technique that combines light excitation and acoustic sensing. This technique allows both good resolution and good tissue penetration. Other techniques are being considered, such as magnetic resonance imaging. However, there are still challenges to be met: the techniques used for these studies, carried out on mice, which have only a few centimeters of tissue, will not necessarily give the resolution expected on humans, at a larger size.

We must therefore not declare victory too quickly. Research is still in its infancy when it comes to micromotors. Many laboratories around the world are developing these robots, but too few are tested on mice and none have yet reached the clinical trial stage. We are therefore impatiently awaiting the development of these medical techniques which might revolutionize non-invasive medicine.

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