Enhancement of oncolytic virotherapy by vanadium(V) dipicolinates Anabel Bergeron . Kateryna Kostenkova . Mohammed Selman . Heide A. Murakami . Elizabeth Owens . Naveen Haribabu . Rozanne Arulanandam . Jean-Simon Diallo . Debbie C. Crans Received: 7 May 2019 / Accepted: 21 May 2019 / Published online: 17 June 2019 Ó Springer Nature B.V. 2019 Abstract Oncolytic viruses rewire the immune system and can lead to long-lasting antitumor defenses against primary and metastatic tumors. However, results from clinical studies have shown heterogeneity in responses suggesting that multiplexed approaches may be necessary to consistently generate positive outcomes in patients. To this end, we explored the combination of oncolytic rhabdovirus VSVD51 with vanadium(V) dipicolinate derivatives, which have already been explored for their antidiabetic properties in animal models. The combination of vanadium- based dipicolinate compounds with VSVD51 signif- icantly increased viral replication and cytotoxicity in the human renal cell carcinoma cell line 786-0. The effects of three vanadium(V)-dipicolinate coordina- tion complexes ([VO 2 dipic] - , [VO 2 dipic-OH] - and [VO 2 dipic-Cl] - with –OH or –Cl in the para position) were compared to that of the simple salts using spectroscopy and speciation profiles. Like the vana- date salts and the vanadyl cation, all dioxovana- dium(V) dipicolinate complexes tested were found to increase viral infection and cytotoxicity when used in combination with VSVD51. Viral sensitization is dependent on the vanadium since free dipicolinate ligands exerted no effect on viral infection and viability. The ability of these complexes to interact with interfaces and the stability of the complexes were evaluated under physiological conditions. Results indicate that these complexes undergo hydrolysis in cell culture media thereby generating vanadate. The vanadium dipicolinate derivatives in the context of immunovirotherapy shares similarities with previous studies exploring the antidiabetic properties of the compounds. The synergy between vanadium com- pounds and the oncolytic virus suggests that these compounds may be valuable in the development of novel and effective pharmaco-viral therapies. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10534-019-00200-9) con- tains supplementary material, which is available to authorized users. A. Bergeron  M. Selman  N. Haribabu  R. Arulanandam  J.-S. Diallo (&) Center for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada e-mail: jsdiallo@ohri.ca A. Bergeron  M. Selman  J.-S. Diallo Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K. Kostenkova  H. A. Murakami  E. Owens  D. C. Crans (&) Department of Chemistry, Colorado State University, Fort Collins, CO, USA e-mail: debbie.crans@colostate.edu D. C. Crans Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO, USA 123 Biometals (2019) 32:545–561 https://doi.org/10.1007/s10534-019-00200-9