there will be a big push to determine the optimal bacterial
strain, payload, circuitry, and appropriate clinical settings in
which to use these types of therapies.Conquering tumors
While researchers are succeeding in engineering bacteria to carry
or produce anticancer compounds, fewer than 1 percent of those
microbes will reach tumors on their own. Since most tumors are not
accessible by direct injection, clinicians need to be able to effectively
navigate bacterial therapies to tumor sites, where the microbes should
reliably and controllably release the toxic drugs they encode.
This is where synthetic biology has been influenced by the
principles of microrobotics. For example, E. coli bacteria can be
engineered with genes from marine microorganisms to sense
and make use of light energy. In 2018, the University of Edin-
burgh’s Jochen Arlt and coworkers showed that such photosyn-
thetic strains of motile E. coli could be guided through spatiallypatterned light fields.^7 In response to patterns of light exposure,
the bacteria moved to certain locations; tracking their position
informed the next light input to guide them forward along a pre-
defined path—a process that’s known as closed loop control, a
fundamental part of robotics.
In the same year, Xian-Zheng Zhang and colleagues at Wuhan
University in China used light to locally trigger a 37-fold increase
in bacterial cytotoxin production by attaching to the bacteria’s
membranes nanomaterials that, upon light exposure, release photo-
electrons that promote the toxin’s synthesis. In a mouse model of
breast cancer, these anaerobic bacteria were found to accumulate in
the hypoxic microenvironment of the tumors, and the subsequent
light-boosted cytotoxin production resulted in around 80 percent
inhibition of tumor growth.^8 This is an example of how the integra-
tion of synthetic material into live bacteria can allow remote con-
trol of certain actions or functionality, another feature borrowed
from classic robotics.
While optically triggered navigation and control has enor-
mous potential, light’s limited ability to penetrate tissue ham-
pers the approach. A more widely used form of external energy
is ultrasound. It has long had applications in medical diagnostics
and monitoring. More recently, gas-filled microbubbles, due to
their strong and distinct acoustic response, are used to enhance
contrast on ultrasound images of tissues, and special forms of high-
powered, focused ultrasound have been applied in therapy to boost
the transport of drug-filled nanobubbles by using the acousticNew genetic toolkits are paving
the way for the emerging fields of
micro- and nanorobotics.
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