Targeted Enzymatic VLP-Nanoreactors with beta-Glucocerebrosidase Activity as Potential Enzyme Replacement Therapy for Gaucher's Disease
Por:
Chauhan, Kanchan, Olivares-Medina, Cindy N., Villagrana-Escareno, Maria V., Juarez-Moreno, Karla, Cadena-Nava, Ruben D., Rodriguez-Hernandez, Ana G., Vazquez-Duhalt, Rafael
Publicada:
6 oct 2022
Resumen:
Gaucher disease is a genetic disorder and the most common lysosomal
disease caused by the deficiency of enzyme beta-glucocerebrosidase
(GCase). Although enzyme replacement therapy (ERT) is successfully
applied using mannose-exposed conjugated glucocerebrosidase, the lower
stability of the enzyme in blood demands periodic intravenous
administration that adds to the high cost of treatment. In this work,
the enzyme beta-glucocerebrosidase was encapsulated inside virus-like
nanoparticles (VLPs) from brome mosaic virus (BMV), and their surface
was functionalized with mannose groups for targeting to macrophages. The
VLP nanoreactors showed significant GCase catalytic activity. Moreover,
the Michaelis-Menten constants for the free GCase enzyme (K-M=0.29 mM)
and the functionalized nanoreactors (K-M=0.32 mM) were similar even
after chemical modification. Importantly, the stability of enzymes under
physiological conditions (pH 7.4, 37 degrees C) was enhanced by
approximate to 11-fold after encapsulation; this is beneficial for
obtaining a higher blood circulation half-life, which may decrease the
cost of therapy by reducing the requirement of multiple intravenous
injections. Finally, the mannose receptor targeted enzymatic
nanoreactors showed enhanced internalization into macrophage cells.
Thus, the catalytic activity and cell targeting suggest the potential of
these nanoreactors in ERT of Gaucher's disease.
Filiaciones:
Chauhan, Kanchan:
Univ Nacl Autonoma Mexico, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
Olivares-Medina, Cindy N.:
Univ Nacl Autonoma Mexico, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
Villagrana-Escareno, Maria V.:
Univ Nacl Autonoma Mexico, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
Juarez-Moreno, Karla:
Univ Nacl Autonoma Mexico, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
Cadena-Nava, Ruben D.:
Univ Nacl Autonoma Mexico, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
Rodriguez-Hernandez, Ana G.:
Univ Nacl Autonoma Mexico, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
Vazquez-Duhalt, Rafael:
Univ Nacl Autonoma Mexico, Ctr Nanociencias & Nanotecnol, Km 107 Carretera Tijuana Ensenada, Ensenada 22860, Baja California, Mexico
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