To
treat cancer, scientists and clinicians have to kill cancer cells while
minimally harming the healthy tissues surrounding them. However,
because cancer cells are derived from healthy cells, targeting only the
cancer cells is exceedingly difficult. According to Dr. Hai-Quan Mao of
the Johns Hopkins University Department of Materials Science and
Engineering, the “key challenge is between point of delivery and point
of target tissue” when it comes to delivering cancer therapeutics. Dr.
Mao spoke about the difficulties of specifically delivering drugs or
genetic material to cancer cells at the 2012 Johns Hopkins University
Nano-Bio Symposium.
Scientists
had originally thought they could create a “magic bullet” to patrol for
cancer cells in the body. However, this has not been feasible; only 5%
of injected nanoparticles reach the targeted tumor using current
delivery techniques. Simply put, scientists need to figure out how to
inject a treatment into the body and then selectively direct that
treatment to cancer cells if the treatments are to work to their full
potential.
With
this in mind, Mao and his research team aim to optimize nanoparticle
design to improve delivery to tumor cells by making the nanoparticles
more stable in the body’s circulatory system. Mao’s group uses custom
polymers and DNA scaffolds to create nanoparticles. The DNA serves dual
purposes, as a building block for the particles and as a signal for
cancer cells to express certain genes (for example, cell suicide genes).
By tuning the polarity of the solvent used to fabricate the
nanoparticles, the group can control nanoparticle shape, forming
spheres, ellipsoids, or long “worms” while leaving everything else about
the nanoparticles constant. This allows them to test the effects of
nanoparticle size on gene delivery. Interestingly, “worms” appear more
stable in the blood stream of mice and are therefore better able to
deliver targeted DNA. Studies of this type will allow intelligent
nanoparticle design by illuminating the key aspects for efficient tumor
targeting.
Currently,
Mao’s group is extending their fabrication methods to deliver other
payloads to cancer cells. Small interfering ribonucleic acid (siRNA),
which can suppress expression of certain genes, can also be incorporated
into nanoparticles. Finally, Mao noted that the “worm”-shaped
nanoparticles created by the group look like naturally occurring virus
particles, including the Ebola and Marburg viruses. In the future, the
group hopes to use their novel polymers and fabrication techniques to
see if shape controls virus targeting to specific tissues in the body.
This work could have important applications in virus treatment.
