Uptake and Intracellular Fate of Cholera Toxin Subunit B-modified Mesoporous Silica Nanoparticle-supported Lipid Bilayers (aka Protocells) in Motoneurons

Overview

Journal Nanomedicine

Publisher Elsevier

Specialties Biomedical Engineering
Biotechnology

Date 2018 Jan 18

PMID 29339186

Citations 7

Authors

Maria A Gonzalez Porras

Paul Durfee

Sebastian Giambini

Gary C Sieck

C Jeffrey Brinker

Carlos B Mantilla

Affiliations

Soon will be listed here.

Abstract

Cholera toxin B (CTB) modified mesoporous silica nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons were examined to provide information for the development of therapeutic application and cargo delivery. Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence techniques, live confocal and transmission electron microscopy, CTB-protocells were primarily found in the cytosol, membrane lipid domains and Golgi. There was no difference in the amount of motoneuron activity dependent uptake of CTB-protocells in neuromuscular junctions, consistent with clathrin activation at the axon terminals during low frequency activity. In conclusion, CTB-protocells uptake is mediated principally by lipid rafts and macropinocytosis. Once internalized, CTB-protocells escape lysosomal degradation, and engage biological pathways that are not readily accessible by untargeted delivery methods.

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