Microsize Molecular Machines Swarm for Drug Delivery

Scientists at Hokkaido University demonstrated light-manipulated microsize molecular machines, or robots, that performed cargo delivery through a swarming strategy to ultimately achieve a transport efficiency 5× greater than that of single robots. The discipline of swarm robotics, which is inspired by the cooperative behavior of living organisms, focuses on the fabrication of robots and their use in swarms to accomplish complex tasks. The cargo used in the team’s experiments consisted of polystyrene beads — laying the application for light-activated microbot swarms to be used in various fields including drug delivery.

Schematic illustrations of cargo transport by a swarm of molecular robots (top) and fluorescence images of a molecular robot transporting blue sphere-like cargo (bottom). The scale bar is 20 μm. By specifying the position of the light irradiation, it is possible to accumulate the cargo at the designated destination (right). The scale bar is 50 μm. Courtesy of Mousumi Akter et al., Science Robotics, April 20, 2022.

A swarm is an orderly collective behavior of multiple individuals, and macro-scale swarm robots have been developed and employed for a variety of applications, such as transporting and accumulating cargo, forming shapes, and building complex structures.

Until now, research has yet to demonstrate the ability of microsize molecular machines to use the advantages of swarming. Due to their size, microrobots and machines at the micro- and nanoscale lack many practical applications. Their ability to cooperate in swarms increases their potential uses.

The team constructed about 5 million single molecular machines. These machines were composed of two biological components: microtubules linked to DNA, which allowed them to swarm, and kinesin, which were actuators capable of transporting the microtubules. The DNA was combined with the light-sensitive compound azobenzene that functioned as a sensor, allowing for control of swarming.

When exposed to visible light, changes in the structure of azobenzene caused the DNA to form double strands and led to the microtubules forming swarms. Exposure to UV light reversed this process.

Pieces of the polystyrene bead cargo ranged in diameter from micrometers to tens of micrometers. The beads were treated with azobenzene-linked DNA. The cargo was loaded when exposed to visible light and unloaded when exposed to UV light. However, the DNA and azobenzene used in the molecular machines and the cargo were different, so swarming could be controlled independently of cargo-loading.

In tests, swarms of machines transported cargo as large as 30 μm in diameter, whereas the single machines loaded and transported the beads up to 3 μm in diameter. Further, a comparison of transport distance and transport volume showed that the swarms were up to 5× more efficient at transport compared to the single machines.

The demonstration that molecular machines can be designed to swarm and cooperate to transport cargo with high efficiency additionally laid the groundwork for microrobot swarms to be used in contaminant collection, molecular power generation devices, and micro-detection devices, said Akira Kagugo, the associate professor from the Faculty of Science at Hokkaido University who co-led the research team.

The research was supported by the Future AI and Robot Technology Research and Development Project from the New Energy and Industrial Technology Development Organization (NEDO); the Ministry of Education, Culture, Sports, Science, and Technology (MEXT); the Grant-in-Aid for Scientific Research on Innovative Areas “Molecular Engine”; and the Grant-in-Aid for Scientific Research.

The research was published in Science Robotics (www.doi.org/10.1126/scirobotics.abm0677).