Researchers in Germany have developed tiny biohybrid robots on the micrometre scale that can swim through the body and deliver drugs to tumours or provide other cargo-carrying functions.
According to researchers from the Max Planck Institute for Intelligent Systems in Stuttgart, the natural environmental sensing tendencies of bacteria mean these microrobots, which are personalised to cater to different circumstances, can navigate toward certain chemicals or be remotely controlled using magnetic or sound signals.
To be successful, these tiny biological robots must consist of materials that can pass clearance through the body’s immune response. They also have to be able to swim quickly through viscous environments and penetrate tissue cells to deliver cargo.
In a paper published in APL Bioengineering, published by the American Institute of Physics (AIP), the researchers describe how they fabricated biohybrid bacterial microswimmers by combining a genetically engineered E. coli MG1655 substrain and nanoerythrosomes, small structures made from red blood cells.
Nanoerythrosomes are nanovesicles derived from red blood cells by emptying the cells, keeping the membranes and filtering them down to nanoscale size. These tiny red blood cell carriers attach to the bacterial membrane using the powerful noncovalent biological bond between biotin and streptavidin. This process preserves two important red blood cell membrane proteins: TER119 needed to attach the nanoerythrosomes, and CD47 to prevent macrophage uptake.
Illustration (top) and scanning electron microscopy image (bottom) of biohybrid bacterial microswimmers, which were fabricated by combining genetically engineered E. coli MG1655 and nanoerythrosomes made from red blood cells. A biotin-streptavidin interaction was used to attach nanoerythrosomes to the bacterial membrane
The AIP said this E. coli MG 1655 serves as a bioactuator, performing the mechanical work of propelling through the body as a molecular engine using flagellar rotation. And as part of the study, the swimming capabilities of the bacteria were assessed using a custom-built 2D object-tracking algorithm and 20 videos taken as raw data to document their performance.
The team found that biohybrid microswimmers with bacteria carrying red blood cell nanoerythrosomes performed at speeds 40 per cent faster than other E. coli-powered microparticles-based biohybrid microswimmers. Furthermore, the work demonstrated a reduced immune response due to the nanoscale size of the nanoerythrosomes and adjustments to the density of coverage of nanoerythrosomes on the bacterial membrane.
These biohybrid swimmers showed the ability to deliver drugs faster, due to their swimming speed, and encounter less immune response, due to their composition.
The researchers plan to continue their work to further tune the immune clearance of the microrobots and investigate how they might penetrate cells and release their cargo in the tumour microenvironment.
“This work is an important stepping stone in our overarching goal of developing and deploying biohybrid microrobots for therapeutic cargo delivery,” said author Metin Sitti. “If you decrease the size of red blood cells to nanoscale and functionalise the body of the bacteria, you could obtain additional superior properties that will be crucial in the translation of the medical micro-robotics to clinics.”
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