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Nanomaterials (Basel). 2019 Apr 23;9(4). pii: E652. doi: 10.3390/nano9040652.

Nanocarriers for Protein Delivery to the Cytosol: Assessing the Endosomal Escape of Poly(Lactide-co-Glycolide)-Poly(Ethylene Imine) Nanoparticles.

Author information

1
Center of Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, 56127 Pisa, Italy. marianna.galliani@sns.it.
2
NEST, Scuola Normale Superiore, 56127 Pisa, Italy. marianna.galliani@sns.it.
3
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy. chiara.tremolanti@phd.unipi.it.
4
Istituto di Fisiologia Clinica, National Research Council, 56124 Pisa, Italy. chiara.tremolanti@phd.unipi.it.
5
Center of Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, 56127 Pisa, Italy. g.signore@fpscience.it.
6
NEST, Scuola Normale Superiore, 56127 Pisa, Italy. g.signore@fpscience.it.
7
Fondazione Pisana per la Scienza ONLUS, 56121 Pisa, Italy. g.signore@fpscience.it.

Abstract

Therapeutic proteins and enzymes are a group of interesting candidates for the treatment of numerous diseases, but they often require a carrier to avoid degradation and rapid clearance in vivo. To this end, organic nanoparticles (NPs) represent an excellent choice due to their biocompatibility, and cross-linked enzyme aggregates (CLEAs)-loaded poly (lactide-co-glycolide) (PLGA) NPs have recently attracted attention as versatile tools for targeted enzyme delivery. However, PLGA NPs are taken up by cells via endocytosis and are typically trafficked into lysosomes, while many therapeutic proteins and enzymes should reach the cellular cytosol to perform their activity. Here, we designed a CLEAs-based system implemented with a cationic endosomal escape agent (poly(ethylene imine), PEI) to extend the use of CLEA NPs also to cytosolic enzymes. We demonstrated that our system can deliver protein payloads at cytoplasm level by two different mechanisms: Endosomal escape and direct translocation. Finally, we applied this system to the cytoplasmic delivery of a therapeutically relevant enzyme (superoxide dismutase, SOD) in vitro.

KEYWORDS:

PLGA nanoparticles; cytosol delivery; endosomal escape; protein delivery; translocation

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