Introduction. Development of efficient non-toxic delivery systems remains a big challenge for targeted cancer therapy. Adenoviral dodecahedron (Dd), a virus-like particle with outstanding cell penetration capabilities, is... [ view full abstract ]
Introduction. Development of efficient non-toxic delivery systems remains a big challenge for targeted cancer therapy. Adenoviral dodecahedron (Dd), a virus-like particle with outstanding cell penetration capabilities, is able to deliver many copies of bioactive molecules into one cell. Cellular and organ tropism evaluation is essential for selecting therapeutic targets for carrier applications. Here we present vector distribution upon intravenous and intratumoral injection in human melanoma xenografts in mice model. Moreover, we demonstrate in vitro analysis of passage accross blood brain barrier (BBB) and Dd translocation between cancer cells.
Methods. To follow Dd distribution in melanoma xenografts 2D fluorescence imaging and real time imaging were used. Dd transport via BBB in MDCKII-MDR1 model was analyzed by Western Blot. To gather the data about cell-to-cell translocation we used fluorescence microscopy.
Results. Upon intratumoural injection, Dd displays over 24-hours persistence in tumours, while nearly no signal is observed in the isolated organs. Intravenous injection results in a spread distribution and the ex vivo imaging of organs and tumours isolated 5 hours after injection shows the highest level of Dd in the liver and the skin. Moreover, ex vivo imaging of isolated brains as well as in vitro analysis in MDCKII-MDR1 model show that Dd is unable to pass through BBB. Results of in vitro studies show that Dd is able to translocate between adjacent cancer cells.
Discussion. Dd persistence in tumour upon intratumoral injection, without spreading on healthy organs suggests that it may be considered as the optimal route of administration in animal studies. Moreover, Dd translocation between neighboring cells, may explain our previous observation, concerning delivery of Dd-drug conjugate to solid tumours in rat model, which resulted in tumour growth inhibition. Dd inability to pass through the BBB on the one hand excludes delivery of factors acting on the central nervous system (CNS), however on the other hand enables therapeutic applications of the carrier, without causing side effects on CNS.
Acknowledgements. This work was financially supported by the National Science Centre (Poland) (DEC-2013/09/B/NZ3/02327)
