by Alexandra Rojek
The mysteries of the brain and its functioning are both an object of fascination for researchers, for the ordinary human, but are also the source of much difficulty in cases of brain cancer. To make a surgeon’s job of removing a cancerous tumor even more difficult than it already inherently is, tumors found in the brain often do not have defined boundaries. In a different type of tumor removal when the surgeon might remove an extra margin of tissue to ensure the complete and successful removal of the tumor, this becomes a much riskier technique for brain tumors when removing such an extra margin since removing any healthy tissue could mean fundamental changes to an individual’s personality or identity, or could lead to severe deficits in their physical functioning.
A neurosurgeon’s task of tumor removal may become much more defined very soon, with the development of Tumor Paint – a dye derived from deathstalker scorpion venom that binds only to cancerous cells, allowing a neurosurgeon to directly see the boundaries of a tumor and to not guess at where the boundary between healthy and cancerous tissue lies.
This tumor paint dye is a fusion of a fluorescent protein, Cy5, with a non-toxic component of this deathstalker scorpion venom, chlorotoxin – together this fusion of the tumor-binding chlorotoxin and fluorescent protein glow when exposed to near-infrared light. The dye can bind to malignant gliomas, medulloblastomas, prostate cancer, intestinal cancer, and sarcoma in mouse models. Incredibly, it can detect small numbers of metastatic cells in the lymph channels, presenting the opportunity to perhaps detect metastases before they localize to secondary sites and become established tumors.1
Beyond being able to ‘paint’ tumor boundaries and aid the difficult and sensitive tasks of surgeons, the promise of chlorotoxin also expands to the delivery of nanoparticles as drug delivery vehicles specifically to cancerous tissue. Chemotherapy is based on the principle that since cancer cells grow and divide faster than healthy cells, they will be more affected by the negative effects of such drugs, but healthy cells are still affected regardless – resulting in the undesirable side-effects of traditional chemotherapy. Being able to deliver drugs, such as through nanoparticles, directly to cancer cells would allow drug discovery to pursue more potent compounds since side-effects would be minimized.
Chlorotoxin has the ability to target cancer cells on its own, and has even been developed as an imaging agent for use in MRI scans to identify tumors, when conjugated with superparamagnetic nanoparticles.2 In further work, it has also been shown that this nanoparticle-conjugated chlorotoxin can inhibit the invasive capacity of tumor cells, suggesting potential therapeutic benefit. The chlorotoxin conjugate was also observed to bind more strongly to cells that exhibited markers correlated with more aggressive and invasive stages of tumors, showing even more promise for its therapeutic applicability.3
What started from deadly scorpion venom inspired development of an injectable dye to identify tumors may be allow the neurosurgeon to become a highly precise painter and hunter of cancerous tissue, holding the promise of transforming some patients’ prognoses – and the boundaries of what it might inspire beyond that are just beginning to be visible on the horizon.
Alexandra Rojek ‘15 is a senior in Currier House, concentrating in Chemical and Physical Biology.
- Veiseh, M. et al. Cancer Res. 2007. 67, 6882-6888.
- Veiseh, O. et al. Nano Lett. 2005. 5,1003-1008.
- Veiseh, O. et al. Small. 2009. 5, 256-264.
Categories: Spring 2015