Nanobiohybrids for the thermoactivation of a therapeutic enzyme by magnetic hyperthermia

Abstract

Due to their size-tunable physical and chemical properties, magnetic nanoparticles (MNPs) have demonstrated a wide range of applications in healthcare and life science. In particular, the well-known property of remotely inducing local heat when an alternating magnetic field (AMF) is applied has opened a new area of research called Magnetic Hyperthermia. Traditionally, the activation of these MNPs as nanoheaters has been used seeking the destruction of tumoral cells. In this work, however, we want to show that it is possible to use the heat generated by AMF for a different purpose: to locally reach an optimal temperature (45ºC) that enhances the conversion of a prodrug (indole-3-acetic acid) into a drug (peroxylated radicals) by a therapeutic enzyme (horseradish peroxidase, HRP). has been optimized. Different biohybrids (biosilica+MNP+HRP) were prepared using polyethylenimines of different molecular weight (1300 and 60000 daltons) as amino catalysts for the formation of the silica nanoparticles. Besides, the combination of enzyme crosslinking and the addition of polyols during encapsulation, provided a 250 times increase in the halflife time of the enzyme at 50°C. After carrying out and extensive physicochemical characterization (SEM, TEM, DLS, SQUID, ICP-OES...), it was demonstrated that by applying AMF it is possible to reach local temperatures higher than 45°C within the enzymes microenvironment without an increase in the overall temperature of the reaction medium. These results show that it is possible to think about developing a novel >on/off> switch approach for the remote conversion of pro-drugs in cancer therapy by enzymes of thermal origin that show little or no activity at 37ºC. This would allow a precise remote control of the therapy that solves a limitation of the current strategies that could not avoid its activation outside the target site.