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

1
Center of Nanotechnology Innovation @NEST, Istituto Italiano di Tecnologia, 56127 Pisa, Italy
2
NEST, Scuola Normale Superiore, 56127 Pisa, Italy
3
Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
4
Istituto di Fisiologia Clinica, National Research Council, 56124 Pisa, Italy
5
Fondazione Pisana per la Scienza ONLUS, 56121 Pisa, Italy
*
Authors to whom correspondence should be addressed.
Nanomaterials 2019, 9(4), 652; https://doi.org/10.3390/nano9040652
Received: 15 March 2019 / Revised: 15 April 2019 / Accepted: 21 April 2019 / Published: 23 April 2019
(This article belongs to the Special Issue Organic Nanomaterials in Biomedicine: Applications and Perspectives)
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. View Full-Text
Keywords: PLGA nanoparticles; endosomal escape; translocation; cytosol delivery; protein delivery PLGA nanoparticles; endosomal escape; translocation; cytosol delivery; protein delivery
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MDPI and ACS Style

Galliani, M.; Tremolanti, C.; Signore, G. Nanocarriers for Protein Delivery to the Cytosol: Assessing the Endosomal Escape of Poly(Lactide-co-Glycolide)-Poly(Ethylene Imine) Nanoparticles. Nanomaterials 2019, 9, 652. https://doi.org/10.3390/nano9040652

AMA Style

Galliani M, Tremolanti C, Signore G. Nanocarriers for Protein Delivery to the Cytosol: Assessing the Endosomal Escape of Poly(Lactide-co-Glycolide)-Poly(Ethylene Imine) Nanoparticles. Nanomaterials. 2019; 9(4):652. https://doi.org/10.3390/nano9040652

Chicago/Turabian Style

Galliani, Marianna; Tremolanti, Chiara; Signore, Giovanni. 2019. "Nanocarriers for Protein Delivery to the Cytosol: Assessing the Endosomal Escape of Poly(Lactide-co-Glycolide)-Poly(Ethylene Imine) Nanoparticles" Nanomaterials 9, no. 4: 652. https://doi.org/10.3390/nano9040652

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