CAMBRIDGE, Mass.--Ultra-small particles loaded with medicine - and aimed with
the precision of a rifle - are offering a promising new way to strike at cancer,
according to researchers working at MIT and Brigham and Women's Hospital.
In a paper to appear the week of April 10 in the
online edition of the Proceedings of the National
Academy of Sciences, the team reports a way to custom
design nanoparticles so they home in on dangerous
cancer cells, then enter the cells to deliver lethal
doses of chemotherapy. Normal, healthy cells remain
The team conducted experiments first on cells growing
in laboratory dishes, and then on mice bearing human
prostate tumors. The tumors shrank dramatically,
and all of the treated mice survived the study; the
untreated control animals did not.
"A single injection of our nanoparticles completely
eradicated the tumors in five of the seven treated
animals, and the remaining animals also had significant
tumor reduction, compared to the controls," said
Dr. Omid C. Farokhzad, an assistant professor at
Brigham and Women's Hospital and Harvard Medical
Farokhzad and MIT Institute Professor Robert Langer
led the team of eight researchers. (Farokhzad was
formerly a research fellow in Langer's lab.)
The scientists said that further testing is needed.
Although all the parts and pieces of their new system
are known to be safe, the system itself must yet
be proven safe and effective in humans. This means
thorough testing must be done in larger animals,
and eventually in humans.
"We're most interested in developing a system that
ends up in the clinic helping patients," Farokhzad
said. To make that happen, he added, "we brought
in cancer specialists and urologists to collaborate
Further, he said, from an engineering perspective "we
wanted to develop a broadly applicable system, one
that other investigators can alter for their own
For example, Langer said, researchers "can put different
things inside, or other things on the outside, of
the nanoparticles. In fact, this technology could
be applied to almost any disease" by re-engineering
the nanoparticles' properties. The nanoparticles
work like a bus that can safely carry different passengers
to different destinations.
In the study, Farokhzad, Langer and colleagues tailor-made
tiny sponge-like nanoparticles laced with the drug
docetaxel. The particles are specifically designed
to dissolve in a cell's internal fluids, releasing
the anti-cancer drug either rapidly or slowly, depending
on what is needed. These nanoparticles were purposely
made from materials that are familiar and approved
for medical applications by the U.S. Food and Drug
Administration. Thus all of the ingredients are known
to be safe.
Also, to make sure only the correct cells are hit,
the nanoparticles are "decorated" on the outside
with targeting molecules called aptamers, tiny chunks
of genetic material. Like homing devices, the aptamers
specifically recognize the surface molecules on cancer
cells, while avoiding normal cells. In other words,
the bus is driven to the correct depot.
In addition, the nanoparticles also display polyethylene
glycol molecules, which keep them from being rapidly
destroyed by macrophages, cells that guard against
foreign substances entering the body.
The team chose nanoparticles as drug-delivery vehicles
because they are so small that living cells readily
swallow them when they arrive at the cell's surface.
Langer said that particles larger than 200 nanometers
are less likely to get through a cell's membrane.
A nanometer is one-billionth of a meter.
The Farokhzad-Langer team created particles that
are about 150 nanometers in size: a thousand sitting
side by side might equal the width of a human hair.
Additional authors of the new paper are Jianjun
Cheng, a former postdoctoral fellow with Langer now
at the University of Illinois; Benjamin A. Teply
of Brigham and Women's Hospital (BWH) and Harvard;
Ines Sherifi, also at BWH and Harvard; Sangyong Jon,
a former postdoctoral fellow with Langer now at the
Gwangju Institute of Science and Technology in South
Korea; Dr. Philip W. Kantoff of the Dana Farber Cancer
Institute; and Dr. Jerome P. Richie of BWH and Harvard.
The research was supported, in part, by a grant
from the National Cancer Institute (NCI) through
the Harvard-MIT Center of Cancer Nanotechnology Excellence.
The Harvard-MIT center is one of seven national Centers
of Cancer Nanotechnology Excellence established recently
by the NCI.
Contact: Elizabeth Thomson
Massachusetts Institute of Technology