Cross Linked Enzyme Aggregates as Versatile Tool for Enzyme Delivery: Application to Polymeric Nanoparticles

Marianna Galliani, Melissa Santi, Ambra Del Grosso, Antonella Cecchettini, Filippo M. Santorelli, Sandra L. Hofmann, Jui Yun Lu, Lucia Angella, Marco Cecchini, Giovanni Signore

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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 encapsulating enzymes with excellent activity retention (usually around 60%), thus leading to functional and targeted nanostructures suitable for enzyme delivery. We then demonstrated that CLEAs NPs efficiently deliver PPT1 in cultured cells, with almost complete enzyme release occurring in 48h. Lastly, we demonstrated that enzymatic activity is fully recovered in primary NCL1 fibroblasts upon treatment with PPT1 CLEAs NPs.

Original languageEnglish (US)
JournalBioconjugate Chemistry
DOIs
StateAccepted/In press - Mar 21 2018

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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  • Cite this

    Galliani, M., Santi, M., Del Grosso, A., Cecchettini, A., Santorelli, F. M., Hofmann, S. L., Lu, J. Y., Angella, L., Cecchini, M., & Signore, G. (Accepted/In press). Cross Linked Enzyme Aggregates as Versatile Tool for Enzyme Delivery: Application to Polymeric Nanoparticles. Bioconjugate Chemistry. https://doi.org/10.1021/acs.bioconjchem.8b00206