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

TL;DR

This study explores how certain chemotherapy drugs interact with an immune-boosting molecule to enhance its stability and effectiveness.

Contribution

The study reveals that tetracycline and anthracycline drugs interact with Poly(I:C) and protect it from degradation.

Findings

All selected chemotherapeutics interact with Poly(I:C) molecules.

Doxycycline and minocycline prolong resistance to RNase cleavage.

Partial protection against degradation was observed in vitro.

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.

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