New magnetic nanoparticles allow researchers to monitor tumor cell suicide occurring in response to anti-cancer drugs.
Many anti-cancer drugs work by inducing apoptosis—controlled cell suicide—in tumor cells. Doctors would benefit from monitoring this apoptosis, in order to assess how well a treatment is progressing and learn how drugs could be improved.
One way to monitor cancer cells is by Magnetic Resonance Imaging (MRI) of magnetic nanoparticles injected into the body. Now Benjamin Thierry at the University of South Australia and co-workers1 have modified magnetic nanoparticles so that they specifically target tumor cells that are undergoing apoptosis.
The researchers discovered that an antibody called 3B9 acts as a good marker of apoptosis caused by chemotherapy. This is because 3B9 attacks La—an antigen that is abundantly expressed in malignant tumors. During apoptosis, La moves from the nucleus to the cytoplasm of cells. At the same time, apoptosis weakens the tumor cell membrane, so the 3B9 antibody can get in and attack La. This process is selective for malignant cells in the late stages of apoptosis.
“We believed that these characteristics would favour 3B9 as an immuno-targeting addition for magnetic nanoparticles,” says Thierry. He and his co-workers managed to attach 3B9 to magnetite nanoparticles that are detectable with MRI.
The researchers first covered the nanoparticles with a dense layer of polyethylene glycol (PEG), which is commonly used to mask drugs and nanoparticles from the immune system. The 3B9 antibody molecules were then attached to the free ends of the PEG molecules (Fig. 1).
The modified nanoparticles bind specifically to La, and resist binding to several other proteins. MRI images showed that the nanoparticles located in the cytoplasm of cells undergoing apoptosis in culture. The team is now testing their probes in animal models. Thierry believes the probes could be more effective and durable than existing targeting mechanisms.
“Most studies to date have used annexin V as a molecular marker of apoptosis, which has largely failed to predict tumour response to chemotherapy,” he says. “3B9 is radically different because it binds late apoptotic tumor cells, particularly after anticancer treatment. Hence, our probes can be used to discriminate between dead cells spontaneously present within tumors and cells that have died as a result of treatment.”
References
Thierry, B., Al-Ejeh, F., Brown, M.P., Majewski, P. & Griesser, H.J. Immunotargeting of functional nanoparticles for MRI detection of apoptotic tumor cells. Adv. Mater. 20 (2008) doi:10.1002/adma.200800998
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Medical diagnosis: Watching cancer kill itself. NPG Asia Mater (2009). https://doi.org/10.1038/asiamat.2009.113
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DOI: https://doi.org/10.1038/asiamat.2009.113