1. Introduction
Breast cancer is the most common malignant tumor worldwide and the
leading cause of female mortality.[1,2] More than
half a million deaths caused by breast cancer were recorded in 2020 by
the Global Cancer Center at WHO.[3] This
histological pathology implies the appearance of adenocarcinoma in
mammary glands.[4] Current therapy for breast
cancer consists of invasive tumor surgical resection and systemic
chemotherapy treatment.[5] However, non-specific
chemo-pharmacologic treatments induce several drastic side
effects.[6,7] Today, nanomedicine is focusing on
designing novel and smart therapies to increase the efficiency of breast
cancer treatment.[8-10]
Glucose oxidase (GOx) enzyme activity has been recently proposed for
cancer nanomedicine applications. GOx, an intracellular enzyme fromAspergillus niger is widely used in glucose determination,
fermentation industry, biosensors fabrication, and as a potential
antibiotic.[11,12] This enzyme catalyzes glucose
oxidation to produce hydrogen peroxide and gluconolactone. In a tumor
environment, the GOx activity reduces, both available glucose and
molecular oxygen, essential compounds for cell metabolism. In addition,
GOx produces oxidative stress generating hydrogen peroxide, killing
tumor cells.[13] Different designs of GOx enzyme
systems have been recently developed for cancer therapy, including
several mono and multimodal vesicles, polymer dots, and magnetic
nanoparticles.[14-17]
Nanoparticle specific-targeting is an emerging field to deliver
cytotoxic activity to tumor cells selectively. The specific
anticancer-drug delivery increases the treatment effectiveness and
reduces the drastic side effects.[18] A diversity
of nanosystems, such as polymer, protein, metallic, organic, and
inorganic nanoparticles, has been proposed for biomedical
applications.[19] Protein cages based on viral
capsids, or virus-like particles (VLPs), are interesting nanosystems
that have been proposed as nanocarriers for delivering anticancer
therapies to specific tumor cells.[20,21] VLPs are
widely used in vaccine technology and have recently recently been
proposed as nanoplatforms as carriers of drugs for different biomedical
therapies.[22-25] VLPs can be derived from native
viruses or obtained by recombinant technology. After removing the
genetic material, the purified monomeric coat protein is self-assembled
under certain conditions forming hollow nanoparticles. Self-assembly
property is used to confine or encapsulate several cargo molecules
producing well-defined symmetry and homogenous size nanoparticles. The
VLPs are highly stable in carrying and delivering cargo molecules, are
biocompatible and biodegradable, and show low
toxicity.[26,27] The surface of VLPs can be
functionalized with a diversity of ligands to be specifically targeted
to cells and tissues [28,29] making smarter and
more efficient therapies. In addition, the suspension of VLPs is highly
stable in biological fluids.
VLPs can contain active enzymes, and the arrangement is called an
enzymatic nanoreactor.[22] Improved catalytic
properties have been reported for virus-based enzymatic
nanoreactors.[30-32] VLP-based enzymatic
nanoreactors containing cytochrome P450 activity have been proposed for
prodrug activation in breast cancer
therapy.[33-35] The protein cage structure
protects the catalytic molecule from protease degradation and decreases
enzyme recognition by the immune system conferring a better catalytic
performance.[36-38] Moreover, the intrinsic porous
structure of the VLP-based nanoreactors can allow the substrates and
products to flow through the system.[39-41]
This work encapsulated glucose oxidase in VLPs from Brome Mosaic Virus
(BMV). The catalytic properties of the enzymatic nanoreactors were
analyzed, and their effect on tumor cell lines was determined.