The team have successfully used the bots to deliver therapeutics that decreases the size of bladder tumours in mice.
"We have designed a single platform that can address all of these problems," says Wei Gao, professor of medical engineering at Caltech, Heritage Medical Research Institute Investigator, and co-corresponding author of the new paper about the bots, which the team calls bioresorbable acoustic microrobots (BAM). "Rather than putting a drug into the body and letting it diffuse everywhere, now we can guide our microrobots directly to a tumour site and release the drug in a controlled and efficient way," Gao says.
In addition, Gao says that the robots have been designed to be bioresorbable, meaning that they leave nothing toxic behind in the body.
The Caltech-developed microrobots are spherical microstructures made of a hydrogel called poly(ethylene glycol) diacrylate. Hydrogels are materials that start out in liquid or resin form and become solid when the network of polymers found within them becomes cross-linked, or hardens. This structure and composition enable hydrogels to retain large amounts of fluid, making many of them biocompatible.
The additive manufacturing fabrication method also enables the outer sphere to carry the therapeutic cargo to a target site within the body.
The hydrogel recipe was created by Caltech researcher Julia R. Greer and her team who specialise in in two-photon polymerisation (TPP) lithography, a technique that uses extremely fast pulses of infrared laser light to selectively cross-link photosensitive polymers according to a particular pattern in a very precise manner.
The technique allows a structure to be built up layer by layer, in a way reminiscent of 3D printers, but in this case, with much greater precision and form complexity.
Greer's team were able to print out microstructur3es that are roughly 30 microns in diameter.
In their final form, the microrobots incorporate magnetic nanoparticles and the therapeutic drug within the outer structure of the spheres. The magnetic nanoparticles allow the scientists to direct the robots to a desired location using an external magnetic field. When the robots reach their target, they remain in that spot, and the drug passively diffuses out.
The exterior of the microstructure is also attracted to water to ensure the robots do not clump together as they travel through the body.
However, the inner surface of the microrobot cannot be hydrophilic because it needs to trap an air bubble, and bubbles are easy to collapse or dissolve.
To ensure the robots are both hydrophilic and hydrophobic, the researchers used a two-step chemical modification.
First, they attached long-chain carbon molecules to the hydrogel, making the entire structure hydrophobic. Then the researchers used a technique called oxygen plasma etching to remove some of those long-chain carbon structures from the interior, leaving the outside hydrophobic and the interior hydrophilic.
The final stage of development involved testing the microrobots as a drug-delivery tool in mice with bladder tumours. The researchers found that four deliveries of therapeutics provided by the microrobots over the course of 21 days was more effective at shrinking tumours than a therapeutic not delivered by robots.
"We think this is a very promising platform for drug delivery and precision surgery," Gao says. "Looking to the future, we could evaluate using this robot as a platform to deliver different types of therapeutic payloads or agents for different conditions. And in the long term, we hope to test this in humans."
