[Catalyst 2019]

Racing towards the
cure for
cancer
By Hannah Boyd
rossing the finish line, Dr. Tour’s
car takes the victory, leading with
Ca margin of about 90 minutes. 1 On
a track of 150 nanometers, six countries
competed in France in 2017 to win the
coveted title. The first of its kind, this race
tested the speed of the smallest cars ever
designed: nanocars. After nearly 20 years of
research, Rice University professor Dr. James
Tour finally created his nanocar, christening
it “the Dipolar Racer”. While winning the
world’s first nanocar race represents an
accomplishment on its own, Tour’s novel
work in nanocar design and synthesis
furthers the discipline of nanoscience
and the manipulation of particles at the
nanoscale.
A working motorized nanocar broke
ground in molecular science, but still
many asked: What next? Inspired by the
nanocar’s molecular motor, Dr. Tour
and his lab group set out to construct
other nanomachines. Nanomachines are
any synthetically designed product that
functions at the nanoscale level. Applying
his synthetic organic research background
to the biological sciences, Dr. Tour, in the
months following the race, began designing
nanomachines which would perforate and
kill target cells. The molecular motors that
once powered the wheels of the tiniest cars
now act as the template for those driving
nanomachines.
The future medicinal application of
nanomachines appears promising. Unlike
widely-used traditional drugs which attack
cells by changing the chemical composition
around them, nanomachines operate
mechanically—leaving behind no chemical
trace. Cells are constantly adapting to their
chemical environments, finding new ways to
survive and building up immunities to each
new drug administered. Where chemical
drugs induce apoptosis (programmed cell
death), perforating cell membranes with
molecular nanomachines induces necrosis
(immediate cell death). Necrosis bypasses
the need for a cell to systematically evaluate
itself before inducing apoptosis. Since cells
cannot adapt to defend against mechanical
damage, nanomachines pave the way for a
class of novel drug designs.
Tour’s nanomachines consist of three
main parts: the fluorophore, rotor, and
the stator. The fluorophore, a particle that
fluoresces when exposed to light, allows
the machines within a sample to be easily
tracked. The rotor, held in place by a stator,
activates and spins when exposed to
ultraviolet light. After the synthesis of the
machines, the first wave of trials tested the
effectiveness and speed of different types
of nanomachines against cell bilayers. To
model targeted cells, researchers used
synthetic bilipid vesicles filled with dye. The
tested nanomachines differed in size and
motor type. After analyzing the data, Tour’s
team found that the smaller machines were
the fastest and most efficient at perforating
the synthetic membranes. 2 The second
wave of trials introduced the nanomachines
to live cells. When exposed to UV light,
the nanomachines induced a substantially
higher rate of necrotic cell death compared
to a control without nanomachines. The
next challenge would be finding a reliable
way to label specific cell to attack. Peptides
can be designed to target specific cellular
recognition sites on different cells, allowing
for the targeted induction of necrosis. After
observing the nanomachines successfully
necrotize live cells, Tour and his group
began studying the effect of adding peptides
to the machine. Matching up with receptors
on the targeted cells, the peptides direct
the machines to the cell that should be
killed. Cell specific death was successfully
observed in live cells when using longer
engineered peptide chains. 2 Being able to
direct the nanomachine to specific markers
on cells allows for huge possibilities within
drug design, especially for the targeting of
cancerous cells.
To test the machine’s effects on live cancer
cell lines, a lab in Durham tested these
molecular machines specific to human
prostate cancer cells in August of 2017.
The nanomachines operated successfully,
inducing cancerous cell-specific necrosis
when activated with ultraviolet light. Detailed
pictures of the process show the membrane
bulge as cytoplasm leaks out of the cells,
dying in as little as one to three minutes. 3
After the publication of these results, many
grew excited towards the potential of a noninvasive
treatment for tumors that resist
chemotherapy.
However, limitations still prevent
nanomachines from clinical implementation.
Tour’s lab group seeks to research methods
that will allow for easier activation of these
machines in vivo. Using ultraviolet light is
disadvantageous when trying to reach cells
within living systems. To offer a solution
to this problem, the group is designing
machines that can be activated by twophoton
absorption or infrared light.4 In
turn, this would allow the activation of
nanomachines past the skin, and aid in the
future directions of using nanotechnology as
a drug treatment for many kinds of cancers.
Work Cited
[1] Davenport, Matt. World’s first nanocar race
crowns champion. Chemical and Engineering
News. 2017, 95, 16-19
[2] Garcia-Lopez, V. et al. Molecular machines open
cell membranes. Nature 548, 567–572 (2017)
[3] Knapton, Sarah. Nanomachines that drill
into cancer cells killing them in just 60 seconds
developed by scientists. Science, 2017.
[4] Williams, Mike. Motorized molecules drill
through cells. Rice News, 2017.
DESIGN BY Abram Qiu
EDITED BY Jenny Wang
Graphic from iStock
18 | CATALYST