Engineering sub-cellular targeting strategies to enhance safe cytosolic silica particle dissolution in cells
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Iturrioz-Rodríguez, Nerea; Correa-Duarte, Miguel Ángel; Valiente Barroso, Rafael; López Fanarraga, MónicaFecha
2020Derechos
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license
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Pharmaceutics, 2020,12(6), 487
Editorial
MDPI
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Palabras clave
Silica Nanocarrier
Cytoplasmic Escape
Biodegradation
Engineering Nanoparticles
HeLa
Motor Neurons
Resumen/Abstract
Mesoporous silica particles (MSP) are major candidates for drug delivery systems due to their versatile, safe, and controllable nature. Understanding their intracellular route and biodegradation process is a challenge, especially when considering their use in neuronal repair. Here, we characterize the spatiotemporal intracellular destination and degradation pathways of MSP upon endocytosis by HeLa cells and NSC-34 motor neurons using confocal and electron microscopy imaging together with inductively-coupled plasma optical emission spectroscopy analysis. We demonstrate how MSP are captured by receptor-mediated endocytosis and are temporarily stored in endo-lysosomes before being finally exocytosed. We also illustrate how particles are often re-endocytosed after undergoing surface erosion extracellularly. On the other hand, silica particles engineered to target the cytosol with a carbon nanotube coating, are safely dissolved intracellularly in a time scale of hours. These studies provide fundamental clues for programming the sub-cellular fate of MSP and reveal critical aspects to improve delivery strategies and to favor MSP safe elimination. We also demonstrate how the cytosol is significantly more corrosive than lysosomes for MSP and show how their biodegradation is fully biocompatible, thus, validating their use as nanocarriers for nervous system cells, including motor neurons.
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