Hepatocellular carcinoma is the most common cancer to strike the liver.
More than 500,000 people worldwide, concentrated in sub-Saharan Africa and Southeast Asia, are diagnosed with it yearly. Most of
those afflicted die within six months.
A big obstacle to treatment of liver cancer is the lack of early diagnosis.
Current techniques, including ultrasound, CT, and MRI scans, spot tumors only
when they have grown to about 5 cm in dia. By that time, the cancer is
especially aggressive, resisting chemotherapy and difficult to remove
Now a research team led by Brown
Univ. reports some
promising results for earlier diagnosis. In lab tests, the team used gold
nanoparticles ringed by a charged polymer coating and an x-ray scatter imaging
technique to spot tumor-like masses as small as 5 mm. The approach, detailed in
marks the first time that metal nanoparticles have been used as agents to
enhance x-ray scattering signals to image tumor-like masses.
“What we’re doing is not a screening method,” said Christoph Rose-Petruck,
professor of chemistry at Brown
Univ. and corresponding
author on the paper. “But in a routine exam, with people who have risk factors,
such as certain types of hepatitis, we can use this technique to see a tumor
that is just a few millimeters in diameter, which, in terms of size, is a
factor of 10 smaller.”
The team took gold nanoparticles of 10 and 50 nm in dia. and ringed them
with a pair of 1-nm polyelectrolyte coatings. The coating gave the
nanoparticles a charge, which increased the chances that they would be engulfed
by the cancerous cells. Once engulfed, the team used x-ray scatter imaging to
detect the gold nanoparticles within the malignant cells. In lab tests, the
nontoxic gold nanoparticles made up just 0.0006% of the cell’s volume, yet the
nanoparticles had enough critical mass to be detected by the x-ray scatter
“We have shown that even with these small numbers, we can distinguish these
[tumor] cells,” Rose-Petruck said.
The next step for the researchers is on the clinical side. Beginning this
summer, the group will attach a cancer-targeting antibody to the nanoparticle
vehicle to search for liver tumors in mice. The antibody that will be used was
developed by Jack Wands, director of the Liver
at Rhode Island Hospital and professor of medical
science at the Warren Alpert Medical School of Brown Univ.
“We have developed a monoclonal antibody that targets a cell surface
protein highly expressed on liver cancer cells,” Wands said. “We plan to couple
the antibody to the gold nanoparticles in an attempt to detect the growth of
early tumors in the liver by x-ray imaging.”
The researchers say the x-ray
scatter imaging method could be used to detect nanoparticle assemblies in other
organs. “The idea should be that if you can figure out to get that
[nanoparticle] to specific sites in the body, you can figure out how to image
it,” said Danielle Rand, a second-year graduate student in chemistry and the
first author on the paper.