Common blood protein combined with nanoparticles kills cancer cells
30 July 2010
A normally benign protein abundant in human blood appears to
be able to zero in on and kill certain cancer cells when paired with
nanoparticles, without having to also load the particles with
The finding could lead to a new strategy for targeted cancer
therapies, according to the University of North Carolina at Chapel
Hill scientists who made the discovery.
However, they also cautioned that the result raises concerns
about unanticipated “off-target” effects when designing nano-delivery
Transferrin, the fourth most abundant protein in human blood, has
been used as a tumour-targeting agent for delivering cancer drugs
for almost two decades. The protein’s receptor is over-expressed on
the surface of many rapidly growing cancers cells, so treatments
combined with transferrin ligands are able to seek out and bind to
them. Nanoparticles infused with transferrin have long been regarded
as safe and nontoxic.
Now, UNC researchers have shown that, surprisingly, attaching
transferrin to a nanoparticle surface can effectively and
selectively target and kill B-cell lymphoma cells, found in an
aggressive form of non-Hodgkin’s lymphoma. It had been thought that
nanoparticles would also need to carry toxic chemotherapy agents to
have such an effect.
The discovery was made by a team of researchers led by Joseph
DeSimone, PhD, Chancellor’s Eminent Professor of Chemistry in UNC’s
College of Arts and Sciences and William R Kenan Jr Distinguished
Professor of Chemical Engineering at North Carolina State
University, along with Jin Wang, PhD, and Shaomin Tian, PhD, in
DeSimone’s lab. Their findings appear in this week’s online issue of
the Journal of the American Chemical Society.
The scientists say the result is an interesting development in
the field of nanomedicine, which researchers hope will eventually
provide widely accepted alternatives, or replacements to
chemotherapay and radiation treatment. Those therapies, while
considered the most effective methods currently available for
tackling cancer, also often damage healthy tissues and organs as a
Using PRINT (Particle Replication in Non-wetting Templates)
technology — a technique invented in DeSimone’s lab that allows
scientists to produce nanoparticles with well-defined size and shape
— the UNC researchers produced biocompatible nanoparticles bonded
with human transferrin, and demonstrated that the particles can
safely and accurately recognize a broad spectrum of cancers. As well
as B-cell lymphoma cells, the particles also effectively targeted
non-small cell lung, ovarian, liver and prostate cancer cells.
Generally, the nanoparticles were non-toxic to such cells and
should therefore be able to be loaded with standard chemotherapy
agents and used to hone in on those cancers.
However, for Ramos cells, an aggressive form of B-cell lymphoma,
the transferrin-bonded PRINT nanoparticles not only recognized them
but also induced cell death. Meanwhile, free transferrin — which was
incubated with Ramos cells but not bound to any nanoparticles — did
not kill any Ramos cells, even at high concentrations.
Researchers are carrying out further studies to determine how and
why the transferrin-carrying nanoparticles proved toxic to the Ramos
cells but not the other tumour types.
“Although this is potentially exciting for the development of
entirely new strategies for treating certain types of lymphomas with
potentially lower side effects, this study also raises concerns for
unanticipated off-target effects when one is designing targeted
chemotherapy agents for other types of cancers,” said DeSimone.