LIGHTING UP TUMORS
A STAR researchers
have developed a hybrid metal-polymer nanoparticle that lights up in the acidic
environment surrounding tumor cells. Nonspecific probes that can identify any
kind of tumor are extremely useful for monitoring the location and spread of
cancer and the effects of treatment, as well as aiding initial diagnosis.
Cancerous tumors
typically have lower than normal pH levels, which correspond to increased
acidity both inside the cells and within the extracellular microenvironment
surrounding the cells. This simple difference between tumor cells and normal
cells has led several research groups to develop probes that can detect the low
pH of tumors using optical imaging, magnetic resonance and positron emission
tomography.
Most of these
probes, however, target the intracellular pH, which requires the probes to
enter the cells in order to work. A greater challenge has been to detect the
difference in extracellular pH between healthy tissue and tumor tissue as the
pH difference is smaller. Success would mean that the probes are not required
to enter the cells.
"Our aim is to
address the challenge of illuminating tumors universally," says Bin Liu
from the A*STAR Institute of Materials Research and Engineering. Liu's team,
together with colleagues from the National University of Singapore, based their
new probe on polymers that self-assemble on gold nanoparticles. The resulting
hybrid structure is not fluorescent at normal physiological pH values: instead
acidic conditions similar to those around tumor cells of approximately pH 6.5
alter chemical groups on the surface of the probes and switch on their
fluorescence.
After validating the
switching mechanism in pH-controlled solutions, the researchers tested the
probes using cultured cells and also in tumor-bearing mice illuminated under
bright light. Twenty-four hours after injection into the mice, obvious and
clear fluorescence was seen only from tumor-bearing tissue, using either
whole-body imaging or examination of removed organs (see image). The ability to
observe the fluorescence of tumors using noninvasive whole-body examination of
living mice indicates the potential of the nanoprobes for use in clinical
situations with human patients.
"Our probes
have so far proved to be biocompatible, which will be crucial for biomedical
applications," says Liu. "We now plan to check further for any
toxicity issues and assess the biological distribution and pharmacological
profile of the probes before hopefully moving on to clinical trials," she
adds. This is the latest of several recent advances in nanoscale medical
technology from Liu's group.
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