Potential Applications of Vanadium-Based Anticancer Drugs for Intratumoral Injections

Injections of highly cytotoxic or immunomodulating drugs directly into the tumor, is a procedure that is increasingly applied in the clinic. Established Pt-based drugs are used in numerous clinical trials using this administration method. Intratumoral administration may also be advantageous for less stable anticancer metal complexes that fail administration by the standard intravenous route. Particularly, hydrophobic metal-containing complexes are taken up rapidly into cancer cells and cause cell death, while the release of their much less toxic decomposition products into the blood has low overall systemic toxicity and, in some cases may even be beneficial. This concept was originally proposed for hydrophobic vanadium(V) (V(V)) complexes with sterically hindered organic ligands, non-innocent Schiff base V(V) catecholato complexes. Several of these classes of complexes were investigated exhibiting a distinct pattern in their potencies against cancer. These complexes were reactive but sufficiently stable and hence survive under physiological conditions and react with the tumor. This strategy can potentially be applied to other metal complexes, such as titanium(IV), gallium(III) and ruthenium(III) complexes, some of which were previously unsuccessful in human clinical trials when administered via intravenous injections. The intratumoral injection potencies can furthermore be improved by delivery of nanocarrier formulations of potent but unstable metal complexes.