A nanotechnology approach to cancer treatment

A nanotechnology approach to cancer treatment


[CHAD] Yet once we did this experiment and saw
for the first time that the spherical nucleic acids not only enter, but are
actively transported, we knew we had something quite special. [LISA] Welcome to Nano
Matters, the podcast that explores specific examples of nanotechnology.
I’m Lisa Friedersdorf, Director of the National Nanotechnology Coordination
Office and here with me today is Chad Mirkin, Director of the International
Institute for Nanotechnology at Northwestern University. So Chad, what is
a cancer immunotherapy or vaccine? [CHAD] So, an immunotherapy is a type of therapy
that trains one’s immune system to fight a specific disease. So vaccine is a class
of immunotherapies. A vaccine is a material that basically trains your
immune system to specifically eradicate a foreign entity, a virus, a bacteria. In the
case of cancer, it would be a type of material that would train your immune
system to specifically eradicate cancer cells, shrink tumors and hopefully cure
the disease. [LISA] So I guess I’ve never thought of a vaccine as training my
immune system. You know, taking my children or if I even remember back to
my own vaccines and shots I got as a child, is that what you do with a cancer
immunotherapy? Is it something like a shot? [CHAD] It’s very similar. It
absolutely is a shot. So in our case, we develop drugs based upon what we call
spherical nucleic acids. These are globular forms of DNA and RNA. And it’s
known through studies of viral and bacterial disease that certain sequences
can stimulate your immune system in a selective way. And so we formulate these
spherical nucleic acids with sequences that are designed to activate your
immune system by engaging with structures called toll-like receptors,
toll-like receptor 9 in particular. That elevates your immune system and when you
combine those types of structures with a peptide, a fragment of a
protein that is a specific signature of the cancer cell, associated the cancer
cell, the vaccine trains your t-cells to go throughout the lymphatic system, find
cells that have that signature and to lyse them. [LISA] So what are the challenges to
developing these immunotherapies and how does nanotechnology play a role? [CHAD] Well nanotechnology is going to play a huge role. I’m convinced of it. In vaccine
development in general, in cancer immunotherapy in particular. We like to
refer to it as rational vaccinology and what I mean by that is what we’ve
discovered through our research is that just taking the components that are
required to create an immunotherapy and injecting them in a black box type of
approach is not good enough. You can sometimes can find materials that that
act as vaccines in that way and in fact we’ve done that predominantly in the
past. But with nanotechnology we’re finding that how you structure the
different components, how you present them to the immune system, can have
dramatic effects on how potent they are. And we have different types of vaccines
that in one format are completely ineffective while in another format are
totally curative. [LISA] So how did you become inspired to work on these globs of DNA,
RNA, these spherical nucleic acids? [CHAD] Well, we invented them. So, almost, well over
20 years ago, we were just playing with nanoparticles and DNA, not trying to
create medicines, not trying to create diagnostic tools, but trying to create
what we call programmable atoms. And we developed the chemistry for interfacing
short snippets of DNA and RNA with spherical nanoparticles. And we developed
the chemistry for loading those short strands of DNA and RNA on the surface
of the particle and in high loadings they are forced to stand upright and
they take on the shape of that central particle core, hence the term spherical
nucleic acid. Those particles actually do act as synthetic atoms. You can kind of
think of them as chemically specific velcro balls. And we learned how to take
different types of spherical nucleic acids and by combining them with partners that they could hybridize with form the
famous double helix, they would bond together and we could build colloidal
crystals from the bottom up. There’s a whole field that focuses on that that’s
become very interesting in its own right. But along the way we discovered that
these globular forms of DNA and RNA had completely different properties from the
normal linear forms of DNA and RNA. So in a sequence for sequence basis, they are
completely different and I’ll give you an example. Normal DNA and RNA will not
enter human cells, where a spherical nucleic acids not only enter, but are
actively taken across the cell membrane. It took us ten years to run that
experiment because we were thinking about these new forms of DNA and RNA as
the old forms and we knew that linear DNA and RNA wouldn’t enter cells. Yet once we did this experiment and saw for the first time that the spherical
nucleic acids not only enter but are actively transported, we knew we had
something quite special and that meant that for the first time we could get
large amounts of DNA and RNA into cells and we could think about using that
capability to make measurements with respect to what’s inside cells, but also
to manipulate how cells function. And that led us down the path of developing
gene regulation tools. That led to a whole series of drugs where we could
regulate gene expression, but it also led to the development of immunotherapies
where we can use globular forms with the right sequences that were designed to
tickle the immune system in a way that would make it useful for vaccine
development. [LISA] Can you share what types of diseases could be impacted by this
approach? [CHAD] Well it’s very exciting! Look six human clinical trials have already
commenced, are either over or currently ongoing, based upon spherical nucleic
acids. They are for diseases like glioblastoma, a deadly form of brain cancer. There are immunotherapies now for treating a wide range of cancers
including deadly forms of skin cancer. There are gene regulation therapeutics
that are designed to knock down inflammatory
markers that are associated with psoriasis and atopic dermatitis. There is
a drug that is designed to reverse the symptoms of young children that suffer
from a disease called SMA, Spinal Muscular Atrophy, a very debilitating
disease and one that really adversely affects young children in very
significant ways. And then there are a whole series of other drugs that are
being developed and tested for a broad range of indications ranging from
diabetic wound-healing to more innocuous things like
coming up with the cure for baldness. [LISA] Also very important. Well I’ve very much
enjoyed talking with you today, do you have any closing thoughts that you want
to share? [CHAD] I think we have to be patient with these types of things, I think
everybody wants a quick fix. They either want to decide something’s no good or
something’s great overnight. In medicine, especially in the area of nanomedicine,
where we’re just learning the rules of the road, we’re gonna have to be patient. But I think if we’re patient, really good things are going to come out of it and
I’m quite confident that we are going to, not only impact the field of medicine,
but I think change how medicine is practiced and certainly how disease is
studied and also how its both diagnosed and treated. And I think that’s exciting.

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