Vault Nanoparticles: Chemical Modifications for Imaging and Enhanced Delivery.
ACS Nano
; 11(1): 872-881, 2017 01 24.
Article
em En
| MEDLINE
| ID: mdl-28029784
ABSTRACT
Vault nanoparticles represent promising vehicles for drug and probe delivery. Innately found within human cells, vaults are stable, biocompatible nanocapsules possessing an internal volume that can encapsulate hundreds to thousands of molecules. They can also be targeted. Unlike most nanoparticles, vaults are nonimmunogenic and monodispersed and can be rapidly produced in insect cells. Efforts to create vaults with modified properties have been, to date, almost entirely limited to recombinant bioengineering approaches. Here we report a systematic chemical study of covalent vault modifications, directed at tuning vault properties for research and clinical applications, such as imaging, targeted delivery, and enhanced cellular uptake. As supra-macromolecular structures, vaults contain thousands of derivatizable amino acid side chains. This study is focused on establishing the comparative selectivity and efficiency of chemically modifying vault lysine and cysteine residues, using Michael additions, nucleophilic substitutions, and disulfide exchange reactions. We also report a strategy that converts the more abundant vault lysine residues to readily functionalizable thiol terminated side chains through treatment with 2-iminothiolane (Traut's reagent). These studies provide a method to doubly modify vaults with cell penetrating peptides and imaging agents, allowing for in vitro studies on their enhanced uptake into cells.
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MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
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Partículas de Ribonucleoproteínas em Forma de Abóbada
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Nanopartículas
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Imagem Óptica
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Corantes Fluorescentes
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article