In a recent study published in “Angewandte Chemie,” researchers report the development of iron oxide nanoparticles capable of self-assembling when placed in a tumor environment. Self-assembly into larger aggregates significantly improved magnetic resonance imaging (MRI) of cancer cells. The research, carried out by a team of scientists at the Imperial College London, has significant implications for the early detection and treatment of cancer.
Visualizing tumors via MRI
MRI offers significant advantages, including high resolution and tissue penetration. What’s more, MRI is noninvasive and does not require the use of ionizing radiation. Its sensitivity, however, is limited.
This limitation can be overcome through the use of contrast agents. Superparamagnetic iron oxide nanoparticles are commonly used for this purpose, due to their biocompatibility and enhancement properties. While larger particles and particle aggregates have a greater effect, they are cleared by the body faster than smaller particles. To overcome this problem, the research team, led by Dr. Eric Aboagye and Dr. Nicholas Long, developed iron oxide particles capable of aggregating only upon encountering a tumor environment.
Cleavage of surface peptides enables self-assembly
Matrix metalloprotein (MMP) enzymes, specifically MMP2 and MMP9 have been shown to play a role in tumor progression. As such, the surface of the iron oxide nanoparticles developed by the Imperial College team contains peptides recognized and cleaved by MMP2 and MMP9. Cleavage exposes specific moieties that chemically react to form covalent bonds. In this way, the particles self-assemble to create nanoclusters that dramatically enhance MRI sensitivity.
In addition to the MMP-cleavable peptides, the iron oxide nanoparticles are coated with a short amino acid sequence that targets them to CXC4R receptors. CXC4R has been used as a predictor of a tumor’s metastatic potential. To enhance biocompatibility, the nanoparticles are coated with polyethylene glycol.
The particles proved capable of enhancing MRI signals when tested in vitro, as well in vivo in mice with tumors expressing a high level of CXC4R. Researchers point out that the implications extend beyond MRI to other applications. Using their design as a model, it is possible to develop magnetic nanoparticles suitable for a number of therapeutic purposes, including targeted delivery of exogenous agents and gene therapy. A full report of their results can be found in the Wiley Online Library.
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