TY - JOUR
T1 - Cross-Linked Enzyme Aggregates as Versatile Tool for Enzyme Delivery
T2 - Application to Polymeric Nanoparticles
AU - Galliani, Marianna
AU - Santi, Melissa
AU - Del Grosso, Ambra
AU - Cecchettini, Antonella
AU - Santorelli, Filippo M.
AU - Hofmann, Sandra L.
AU - Lu, Jui Yun
AU - Angella, Lucia
AU - Cecchini, Marco
AU - Signore, Giovanni
N1 - Funding Information:
This work was in part supported by Fondazione Cassa di Risparmio di Lucca through the project “Pre-Clinical Testing of Lithium treatment in Krabbe Disease” and by ELA International through the project “Development of a novel, nanovector-mediated enzyme replacement therapy for Globoid Cell Leukodystrophy.”
Publisher Copyright:
Copyright © 2018 American Chemical Society.
PY - 2018/7/18
Y1 - 2018/7/18
N2 - Polymeric nanoparticles (NPs) represent one of the most promising tools in nanomedicine and have been extensively studied for the delivery of water-insoluble drugs. However, the efficient loading of therapeutic enzymes and proteins in polymer-based nanostructures remains an open challenge. Here, we report a synthesis method for a new enzyme delivery system based on cross-linked enzyme aggregates (CLEAs) encapsulation into poly(lactide-co-glycolide) (PLGA) NPs. We tested the encapsulation strategy on four enzymes currently investigated for enzyme replacement therapy: palmitoyl protein thioesterase 1 (PPT1; defective in NCL1 disease), galactosylceramidase (GALC; defective in globoid cell leukodystrophy), alpha glucosidase (aGLU; defective in Pompe disease), and beta glucosidase (bGLU; defective in Gaucher's disease). We demonstrated that our system allows encapsulation of enzymes with excellent activity retention (usually around 60%), thus leading to functional and targeted nanostructures suitable for enzyme delivery. We then demonstrated that CLEA NPs efficiently deliver PPT1 in cultured cells, with almost complete enzyme release occurring in 48 h. Finally, we demonstrated that enzymatic activity is fully recovered in primary NCL1 fibroblasts upon treatment with PPT1 CLEA NPs.
AB - Polymeric nanoparticles (NPs) represent one of the most promising tools in nanomedicine and have been extensively studied for the delivery of water-insoluble drugs. However, the efficient loading of therapeutic enzymes and proteins in polymer-based nanostructures remains an open challenge. Here, we report a synthesis method for a new enzyme delivery system based on cross-linked enzyme aggregates (CLEAs) encapsulation into poly(lactide-co-glycolide) (PLGA) NPs. We tested the encapsulation strategy on four enzymes currently investigated for enzyme replacement therapy: palmitoyl protein thioesterase 1 (PPT1; defective in NCL1 disease), galactosylceramidase (GALC; defective in globoid cell leukodystrophy), alpha glucosidase (aGLU; defective in Pompe disease), and beta glucosidase (bGLU; defective in Gaucher's disease). We demonstrated that our system allows encapsulation of enzymes with excellent activity retention (usually around 60%), thus leading to functional and targeted nanostructures suitable for enzyme delivery. We then demonstrated that CLEA NPs efficiently deliver PPT1 in cultured cells, with almost complete enzyme release occurring in 48 h. Finally, we demonstrated that enzymatic activity is fully recovered in primary NCL1 fibroblasts upon treatment with PPT1 CLEA NPs.
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U2 - 10.1021/acs.bioconjchem.8b00206
DO - 10.1021/acs.bioconjchem.8b00206
M3 - Article
C2 - 29894633
AN - SCOPUS:85048703988
SN - 1043-1802
VL - 29
SP - 2225
EP - 2231
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 7
ER -