Wouldn't it be nice if we could detect tumors and their metastases as easily
as we find broken bones with X-rays? A team of scientists headed by S. Bhatia
in Boston (USA) has been working on this problem. They have found a way to
make a tumor-specific protease visible by using Fe 3 O 4 nanoparticles and
magnetic resonance imaging (MRI).
Organic tissue is mostly made of water and fat,
substances that contain many protons (positively
charged hydrogen ions or hydrogen nuclei). These
have an intrinsic angular momentum, known as spin,
and thus a magnetic moment. In a magnetic field,
they line up and rotate with a certain frequency
that is proportional to the strength of the external
field. If electromagnetic waves with the same frequency
(resonance) are beamed in, they disturb the orientation
of the protons in the external material field. When
the electromagnetic wave is switched off, the protons
flip back to their original position, which causes
them to give off an electromagnetic signal of their
own. This can be detected and gives information about
the proton density and the chemical environment in
the region being studied. These data allow for the
computation of a 3D image that depicts the different
tissues in the body.
How can this be used to detect mutated cells with
the best possible resolution and high confidence?
The Boston researchers used nanoparticles of Fe 3
O 4 whose magnetic properties change when they aggregate
into large multimeric complexes.
Two biomolecules that bind to each other with high
affinity, biotin and neutravidin, act as a “glue” to
hold the Fe 3 O 4 particles together. Half of the
nanoparticles are coated with biotin, the other half
with neutravidin. Long polyethylene glycol (PEG)
chains are coupled to these biomolecules in order
to keep the particles from interacting with each
other. The anchor for the PEG chains is a peptide
that contains a segment that can be cleaved by a
tumor-specific enzyme, matrix metalloproteinase-2
(MMP-2).
MMP-2 is mostly found in the immediate area around
growing tumor cells, meaning that the PEG chains
are only cleaved from the Fe 3 O 4 nanoparticles
when they are near a tumor. This then allows the
biotin–neutrovidin glue to do its job—the Fe 3 O
4 particles aggregate and the tumor becomes visible
in the MRI image.
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Author: Sangeeta N. Bhatia, Massachusetts Institute
of Technology, Cambridge (USA), http://lmrt.mit.edu/personnel/sangeeta.asp
Title: Proteolytic Actuation of Nanoparticle Self-Assembly
Angewandte Chemie International Edition 2006 , 45 ,
No. 19, 3161–3165, doi: 10.1002/anie.200600259
The original article and the annotated table of contents
of the upcoming issue are available ahead of publication from our online pressroom
at http://pressroom.angewandte.org .
Contact : Editorial office: angewandte@wiley-vch.de or
David Greenberg (US): dgreenbe@wiley.com or
Julia Lampam (UK): jlampam@wiley.co.uk
Angewandte Chemie International Edition ,
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