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Novel Vanadium Complexes to Treat Solid Tumors

At a Glance

​Researchers at Colorado State University in collaboration with University of Sydney have developed novel Vanadium (V) complexes to treat highly aggressive brain cancer via intra-tumoral injection.  Preliminary data in various human cancer cell lines (typically treated by intra-tumoral injections) indicate the novel V Complexes have higher cytotoxicity, increased stability and permeability in cell membranes as compared to the anti-cancer drug cisplatin.  Furthermore, the V Complexes are consistently more toxic to cancer cells vs. non-cancer cells.

Background

Novel therapeutics are required for difficult-to-treat cancers, including brain, lung and pancreatic cancers, in which stabilized formulations of strongly cytotoxic or immune-modulating drugs are injected directly into the tumor. Metal-based drugs, including vanadium (V) complexes, in combination with novel delivery techniques, are promising for such purposes. Although the enhancement of oncolytic viruses by V compounds have shown a remarkable selectivity for cancerous tissue over normal tissue, the extensive reactivity of V complexes in biological media and associated toxicity has been a large hinderance to their use.

Such drugs begin to kill cancer cells immediately after injection into tumors, while their decomposition products released into the blood are less toxic – which is expected to reduce systemic toxicity, a major problem of cancer chemotherapy. Furthermore, decomposition products are likely to prove beneficial, given known anti-diabetic, anti-mutagenic, tissue regeneration promoting and neuro-stimulatory properties of V compounds, all of which can provide simultaneous benefits to many patients.

Overview

The newly developed Vanadium complexes have shown much greater promise. These compounds are more hydrophobic, more hydrolytically stable, more easily reduced compared to their correspond

ing parent counterparts, and may contain potent in vitro anti-cancer activity that is 10 times more potent than cisplatin (chemotherapy gold standard) under the same conditions.

Shown below in Figure 1 is the cell viability of human glioblastoma multiforme (T98g) cells, an in vitro model of brain gliomas when treated with a Vanadium (V) complex that was freshly prepared or aged for 24 hours in biological media. As shown, the V complex proved to be highly cytotoxic to the cancer cells, and produced a lower IC50 for the fresh solution as compared to a 24-hour aged solution.

A graph showing the anticancer effects of the new vanadium complex
Figure 1

Benefits

  • Non-toxic decomposition products (i.e., decreased toxicity as compared to cisplatin)
  • Increased stability of both anticancer drug and the side products
  •  Increased permeability in cell membranes
  • V complex shows immediate death of targeted cells
  • Direct injections into tumors allow the use of highly cytotoxic drugs

Applications

  • Treatment of particularly difficult cancers, e.g. brain cancer
  • Solid tumor treatment

Publications

Levina, A, et al. 2020. A Short-Lived but Highly Cytotoxic Vanadium(V) Complex as a Potential Drug Lead for Brain Cancer Treatment by Intratumoral Injections. Angewandte Chemie International Edition. DOI: 10.1002/anie.202005458

Crans, D., et al. 2019. Hydrophobicity may enhance membrane affinity and anti-cancer effects of Schiff base vanadium(v) catecholate complexes. Dalton Trans. 48, 6383-6395 DOI: 10.1039/c9dt00601j

Crans. D. et al. 2023. Vanadium(V) pyridine-containing Schiff base catecholate complexes are novel lipophilic, redox-active and selectively cytotoxic in glioblastoma (T98g) cells. Chem. Eur J. DOI: https://doi.org/10.1002/chem.202302271

Last Updated: October 2023
Opportunity

Available for Licensing
TRL: 2

IP Status

US Utility Patent

Inventors

Debbie Crans
Peter Lay

Reference Number
2023-012
Licensing Manager

Steve Foster
Steve.Foster@colostate.edu
970-491-7100

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