Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons

Maria A. Gonzalez Porras, Paul Durfee, Sebastian Giambini, Gary C Sieck, C. Jeffrey Brinker, Carlos Bernardo Mantilla

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)661-672
Number of pages12
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number3
DOIs
StatePublished - Apr 1 2018

Keywords

  • Cholera toxin subunit B
  • Lipid raft endocytosis
  • Macropinocytosis
  • Mesoporous silica nanoparticles
  • Motoneuron
  • Neuromuscular junction

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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