Ultrasound-triggered vaporization of a perfluorocarbon compound loaded into microbullets provides the necessary force for the microbullets to penetrate, cleave, and deform cellular tissue for potential targeted drug delivery and precision nanosurgery. The microbullets have an inner Au layer that allows conjugation of a monolayer of thiolated cysteamine (green in picture) for electrostatic attachment of perfluorocarbon droplets (purple droplets).
small submarines that can swim through our blood to clear out clogged
arteries or destroy malignant tumors. This concept may sound utopian,
but it isn’t. Various micro- and nanomachines have in fact already been
developed. In the journal Angewandte Chemie, American researchers have
now introduced a new type of machine that finally has enough propulsive
power to penetrate tissue and overcome cellular barriers.
approaches suffered from the fact that the tiny machines didn’t have
enough power or lacked biocompatibility. A team led by Sadik Esener and
Joseph Wang at the University of California, San Diego has now overcome
this challenge. Their new type of micromachine owes its amazing power to
ultrasound, which explosively vaporizes tiny drops of liquid,
accelerating the machines like bullets.
novel “microbullets” are conical, pointed, gold-coated tubes with
dimensions on the micrometer scale. Their interior is additionally
coated with a special biocompatible substance that is capable of binding
tiny drops of emulsion through electrostatic interactions. The emulsion
used is based on biocompatible perfluorocarbon compounds. An additional
magnetic component (nickel) ensures that an external magnetic field can
be used to direct the tube to the desired location and orientation.
ultrasound is then directed at this location, the drops are explosively
vaporized. Like bullets in a gun barrel, the tubes are pushed forward
by the microexplosion. Depending on the dimensions of the tubes, the
size and composition of the emulsion drops, and the strength of the
ultrasound signal, speeds around 6.3 m/s can be attained. This is about
one hundred times faster than previously reported micromachines, and is
enough to shoot the tiny bullets into tissues. Because the fuel is “on
board”, propulsion is independent of the environment.
are a wide variety of possible applications: microbullets could be used
to drive drugs deep into diseased tissue, shoot genes into cell nuclei
for gene therapy, scrape deposits off of arterial walls, shoot antitumor
drugs directly into a tumor, or even carry out micro-operations.
first area of application may be local stimulation of the immune system
for fighting bladder cancer. In conventional treatment, a weakened form
of the bacterium that causes tuberculosis is introduced to the bladder,
causing a superficial bladder infection. This activates the immune
system, which attacks the tumor cells as well as the tuberculosis
bacteria. Instead of this approach, the microbullets could be shot into
the bladder wall to initiate the desired inflammatory reaction – without
the risks and side effects associated with the bacteria.
Droplet Vaporization and Propulsion of Perfluorocarbon-Loaded
Microbullets for Targeted Tissue Penetration and Deformation