Interaction of Selected Anthracycline and Tetracycline Chemotherapeutics with Poly(I:C) Molecules

Abstract

Despite the natural ability of the immune system to recognize cancer and, in some patients, even to eliminate it, cancer cells have acquired numerous evading mechanisms. With the increasing knowledge and focus shifting from targeting rapidly proliferating cells with chemotherapy to modulating the immune system, there have been recent efforts to integrate (e.g., simultaneously or sequentially) various therapeutic approaches. Combining the oncolytic activity of some chemotherapeutics with immunostimulatory molecules, so-called chemoimmunotherapy, is an attractive strategy. An example of such an immunostimulatory molecule is polyinosinic:polycytidylic acid [Poly(I:C)], a synthetic analogue of double-stranded RNA characterized by rapid nuclease degradation hampering its biological activity. This study investigated the possible interactions of tetracycline and anthracycline chemotherapeutics with different commercial Poly(I:C) molecules and protection against nuclease degradation. Fluorescence spectroscopy and circular dichroism revealed an interaction of all of the selected chemotherapeutics with Poly(I:C)s and the ability of doxycycline and minocycline to prolong the resistance to RNase cleavage, respectively. The partial protection was observed in vitro as well.