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Photo activated cancer prodrug

Technology Overview:
Researchers at Leiden University in collaboration with researchers from Texas State University have developed a novel photo activated anticancer prodrug. This prodrug consists in a rigidin analogue caged by a ruthenium polypyridyl complex that can be released upon green light irradiation. The photocaged rigidin inhibitor is a microtubule polymerization inhibitor, and as such disrupts the formation of tumor vasculature.

Microtubule-targeting agents have been used in clinic for over 50 years, but they can be very toxic for the patient. The successful caging and release upon irradiation of the inhibitor means that it is now possible to keep the systemic concentration of the (pro)drug at a higher level than the level of toxicity, without such a high concentration causing significant biological effects. By shining light at the tumour site, a high dose of the inhibitor is only released locally (or in other words, the caged inhibitor is “hidden” in the dark).

Because the agent activation is irreversible, activity will be retained after light irradiation has been removed. Also, unlike in photodynamic therapy, where oxygen concentration in the irradiated tumor should be high enough, these new compounds remain active under hypoxic conditions (1% oxygen) as their activation mechanism does not rely on the presence of dioxygen.

Finally, attachment of the ruthenium-based caging significantly increases the water solubility of the drug in the dark.

Potential applications:

  • Cancer therapy

State of development:

The 7-deazahypoxanthine synthetic analogues of marine alkaloid rigidins have shown promising anticancer activities; they were found to be highly effective in eradicating cancer cells in cell cultures at low doses (double- to single-digit nanomolar antiproliferative IC50 values) and showed statistically significant tumor size reduction in a colon cancer mouse model at nontoxic concentrations.

Opportunity:

The researchers are looking for partners from industry to take this invention to the next stage, which would be to carry out extensive in vivo (mouse model) studies.

IP Status:

The rigidin analogues have been patented by New Mexico Tech and Texas State University jointly, while a patent application has been filed for the caging technology by Texas State University and Leiden University jointly.

Further information

Ellen Willemse Knowledge Broker (LU) +31-71-527 2533 +31-6-1422 8005 e.s.m.willemse@luris.nl