Light-controlled organic microswimmers for on-the-spot drug delivery

Microrobots, which are propelled by light and flow through blood or other fluids in human bodies, can deliver pharmaceuticals to cancer cells and drop off the medication on the spot, according to science fiction novelists. What appears to be a fantastical scenario is really a brief account of a research endeavour published in the journal Science Robotics. The microswimmers described in this paper have the ability to execute activities in living creatures or biological environments that would otherwise be difficult to access. Looking even farther forward, the swimmers may one day be able to aid in the treatment of cancer and other disorders.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) and its neighbouring institute, the Max Planck Institute for Solid State Research (MPI-FKF), demonstrate organic microparticles that can steer through biological fluids and dissolved blood in an unprecedented way in their paper "Light-driven carbon nitride microswimmers with propulsion in biological and ionic media and responsive on-demand drug delivery." The microswimmers can be driven forward at high speeds by visible light, either individually or as a swarm, even in very salty liquids. They are also somewhat biocompatible and have the ability to take up and release cargo on demand. Scientists from MPI-Physical IS's Intelligence Department, directed by Metin Sitti, and MPI-Nanochemistry FKF's Department, led by Bettina Lotsch, were involved.

Until now, designing and constructing such advanced microswimmers seemed unattainable. The salts in water or the body obstruct the movement of light energy. This necessitates a complex design that is difficult to scale. Furthermore, commanding the robots from the outside is difficult and often expensive. Another outstanding discipline in the field of nanorobotics is controlled cargo uptake and on-the-spot distribution.

The researchers utilised a porous two-dimensional carbon nitride (CNx) that may be made from organic compounds such as urea. Carbon nitride, like the solar cells in a photovoltaic panel, can absorb light and use it to move the robot forward when light illuminates the particle surface.

"When doing research in a petri dish or for applications directly under the skin, using light as the energy source of propulsion is quite easy," explains Filip Podjaski, a group leader in MPI-Nanochemistry FKF's Department. "There's just one problem: even very small concentrations of salts prevent light-controlled motion. Salts are found in all biological liquids: blood, cellular fluids, digestive fluids, and so on. However, we've demonstrated that our CNx microswimmers work in all biological liquids — even when the concentration of salt ions is very high." This is only achievable because of a favourable interplay of elements, including efficient light energy conversion as the driving force, as well as the porous structure of the nanoparticles, which allows ions to pass through them, effectively lowering the resistance generated by salt. Furthermore, light favours ion mobility in this material, making the particle even quicker."

After proving the swimmers' salt tolerance, the researchers took on the task of using them as medication carriers. Varun Sridhar notes, "This is also feasible due to the material's porosity." He is the first author of the paper and a postdoctoral researcher at MPI-IS. He and his team injected the anti-cancer medicine Doxorubicin into the swimmers' tiny pores. "The particles soaked up the medication like a sponge, absorbing up to 185 percent of the carrier mass while remaining securely linked to the carbon nitride for more than a month. We then demonstrated that regulated medication release is possible in an acidic pH solution. Furthermore, regardless of a change in pH, we were able to illuminate the microswimmers and therefore release the medication. Even when fully laden, the swimmer did not noticeably slow pace, which is fantastic."

It's difficult to release the drug cargo in a regulated and efficient manner at the appropriate location. When the medication comes into contact with acidic conditions, such as those found in the stomach, it is rapidly desorbed in large volumes. This commonly observed scenario of severe pH shifts, on the other hand, is not found in other areas of the body or biological surroundings. As a result, additional external release triggers are required.

"We discovered that the illumination with blue light, which enables propulsion, also releases the medication carried," adds Podjaski. "This isn't necessarily desirable for focused applications, as drug release would occur along the particle's whole path of travel. The intrinsic charging capabilities of our novel carbon nitride comes into play here: when illuminated in oxygen-depleted (hypoxic) settings, the material may charge up, accumulating the light energy intrinsically, similar to a solar battery we previously discussed. When the particle becomes charged under such hypoxic conditions, the interactions with the adsorbed medicines are altered, and drug release is greatly increased, allowing for an efficient action on cells. As a result, the material's light charging ability, which is influenced by hypoxia, transforms into a detecting property for the release."

In an experiment with genuine tumour cells, the researchers were able to demonstrate this relationship. The researchers describe how they lighted Doxorubicin-loaded carbon nitride particles in the presence of cancer cells, how the drug is released and taken up by the cells, and how the drug causes the cells to decay in their study.

"Our research demonstrates how much untapped potential exists in exploiting well-known, easily synthesizable, plentiful, and porous microparticle materials, which are generally used in photocatalysis, as microrobot materials," explains Metin Sitti.

"The intrinsic characteristic of porous organic materials allows for enormous inner volumes and surface areas, allowing for plenty of cargo room while circumventing constraints on light propulsion that would otherwise be faced in the presence of ions." Further tailoring of molecular locations could enable more regulated cargo interactions without the use of difficult-to-control encapsulation structures or unique shape design. Finally, using environmentally sensitive property changes affecting optoelectronic material properties, as provided by our material's inherent photo charging abilities, appears to be an efficient pathway for designing not only controllable, but also semi-autonomously acting cargo carriers," Bettina Lotsch says.

Although microswimmers are a vision of the future that will only work in ideal conditions, the study's basic research could pave the way for light-controlled and biocompatible materials, as well as intelligent semi-autonomous systems with applications in other fields. "We aim to encourage a lot of smart people to come up with even better techniques to control microrobots and build a responsive function for the benefit of our society," Sitti says.

Reference:

Varun Sridhar, Filip Podjaski, Yunus Alapan, Julia Kröger, Lars Grunenberg, Vimal Kishore, Bettina V. Lotsch, Metin Sitti. Light-driven carbon nitride microswimmers with propulsion in biological and ionic media and responsive on-demand drug delivery. Science Robotics, 2022; 7 (62) DOI: 10.1126/scirobotics.abm1421