DOI: https://doi.org/10.29363/nanoge.amamed.2022.020
Publication date: 22nd April 2022
Anti-cancer drugs are usually associated with lack of specificity and high systemic toxicity. Thus, new strategies are needed for reducing these side effects. Among them, enzyme prodrug therapy is one of the latest. It is based on the conversion of a low toxicity molecule into a cytotoxic agent only in presence of a specific enzyme.
Here, we propose an enzyme-nanoparticles hybrid that synergistically integrate the specific recognition, selectivity, and unique catalytic properties of enzymes with the size-dependent unique features of nanomaterials. In this sense, we have co-entrapped magnetic nanoparticles (MNPs) with a therapeutic enzyme (Horseradish Peroxidase, HRP) in a biomimetic silica matrix in mild and biocompatible conditions [1] to exploit the HRP activity on an innocuous pro-drugthat induces oxidative stress over tumour cells and the possibility of MNPs to generate heat under an alternative magnetic field.
The nanohybrids (nHs) display good co-entrapment efficiencies in terms of HRP immobilization (62 ± 6 %), expressed activity (79 ± 15 %) and entrapped iron (80 ± 6 %) and good catalytic properties. Besides, we assure a time-controlled activation of the enzyme, and thus of the cytotoxic effect, by a remote enzymatic nanoactuation. Indeed, in vitro results with nHs show that the system is not cytotoxic per se and displays enhanced cytotoxic activity only in the presence of the prodrug and the AMF application towards a pancreatic cancer cell line.
The research for this work has received funding from the European Union (EU) project HOTZYMES (grant agreement n° 829162) under EU’s Horizon 2020 Programme Research and Innovation actions H2020-FETOPEN-2018-2019-2020-01. Authors also thank Spanish MINECO project BIO2017-84246-C2-1-R, DGA and Fondos Feder (Bionanosurf E15_17R). Author is grateful for a predoctoral fellowship FPU (FPU19/01311).
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