Algae micromotors join the ranks for targeted drug delivery

Fast-swimming algae can carry drugs to where they are needed in the body to fight disease. In two new studies conducted in mice, researchers have used algae micromotors to deliver antibiotics to the lungs to treat pneumonia (Nat. Mater. 2022, DOI: 10.1038/s41563-022-01360-9) and a simulated chemotherapy drug to the gastrointestinal tract (Sci. Robot. 2022, DOI: 10.1126/scirobotics.abo4160).

These living microbots should be safer for clinical use compared to previously reported synthetic drug delivery nanomotors, says study coauthor Joseph Wang, a nanoengineer at the University of California, San Diego. “The beauty is that it’s all biocompatible, so there is no concern of safety or toxicity.”

Delivering drugs to targeted sites in the body is an approach that fights disease more effectively and helps minimizes side effects. Over the past decade, researchers have made tiny robots that can cruise around the stomach and gastrointestinal tract, powered by zinc- or magnesium-based motors. To make more biocompatible systems, some teams have hitched drug payloads to bacteria and sperm to take advantage of their natural swimming abilities.

Microalgae are much faster swimmers. So Wang, Liangfang Zhang of UCSD, and their colleagues harnessed one type that whips its two hairlike appendages to move at speeds as fast as 200 µm/s, eight times as fast as sperm.

They attached drug-filled polymer nanoparticles onto the surface of the algae using click chemistry, the 2022 Nobel Prize-winning method that uses fast, selective reactions to link molecules. The biodegradable nanoparticles are coated with white blood cell membranes. By mimicking immune cells in this way, the particles can evade attacks from the body’s immune system and attack bacteria to fight infection.

In one study, the team injected thousands of nanoparticle-bearing algae into the windpipes of mice infected with deadly pneumonia. The algae spread through the lung tissue, moving around for at least 24 h delivering antibiotics as the polymer particles dissolved. All the mice treated with the algae motors survived. By contrast, only one-quarter of the mice that received nanoparticles alone survived, and untreated mice died within 3 days. Mice given intravenous injections of the drug alone also survived, but they needed a dose 3,000 times as high as the microbot therapy.

The group’s other study demonstrated the use of algae to carry orally-administered medication through the stomach and into the intestines. For this, the researchers first encased nanoparticle-loaded algae in protective capsules made of a pH-sensitive polymer.

The capsule protects the algae from the acidic environment of the stomach but dissolves in the near-neutral pH of intestinal fluids, releasing swarms of algae that swim around for hours delivering their payloads. The researchers used fluorescent dyes and a chemotherapy drug stimulant for their tests. They plan to do more clinically relevant tests with actual drugs soon.

The previous microbots powered by zinc- or magnesium-based motors last for just a few hours in the gastrointestinal tract tract. The algae, meanwhile, can propel themselves for 24 h, Wang says.

Using algae’s natural swimming ability as a better way to distribute drugs is a novel idea, says Mark R. Prausnitz, a chemical and biomolecular engineer at Georgia Institute of Technology. More work will be needed to determine if algae motors can improve drug therapy in a diseased intestine and to expand the work to larger animals and eventually humans, he says. But drug delivery using microorganisms has a big advantage compared to physical and chemical methods. “This avoids the need for complex instrumentation, embedded power sources, and possible toxicity,” Prausnitz says. “Nature provides us with algae cells that serve as robots.”