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Open AccessArticle

Engineering Sub-Cellular Targeting Strategies to Enhance Safe Cytosolic Silica Particle Dissolution in Cells

1
Grupo de Nanomedicina, Instituto Valdecilla-IDIVAL, Herrera Oria s/n, 39011 Santander, Spain
2
Biomedical Research Centre (CINBIO), Universidade de Vigo, 36310 Vigo, Spain
3
Southern Galicia Institute of Health Research (IISGS), and CIBERSAM, 36213 Vigo, Spain
4
Departments of Applied Physics, University of Cantabria, 39005 Santander, Spain
5
Molecular Biology, University of Cantabria, 39011 Santander, Spain
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 487; https://doi.org/10.3390/pharmaceutics12060487
Received: 8 April 2020 / Revised: 21 May 2020 / Accepted: 26 May 2020 / Published: 28 May 2020
(This article belongs to the Special Issue Silica Nanoparticles for Delivery of Therapeutics and Imaging Agents)
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. View Full-Text
Keywords: silica nanocarrier; cytoplasmic escape; biodegradation; engineering nanoparticles; HeLa; motor neurons silica nanocarrier; cytoplasmic escape; biodegradation; engineering nanoparticles; HeLa; motor neurons
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MDPI and ACS Style

Iturrioz-Rodríguez, N.; Correa-Duarte, M.Á.; Valiente, R.; Fanarraga, M.L. Engineering Sub-Cellular Targeting Strategies to Enhance Safe Cytosolic Silica Particle Dissolution in Cells. Pharmaceutics 2020, 12, 487. https://doi.org/10.3390/pharmaceutics12060487

AMA Style

Iturrioz-Rodríguez N, Correa-Duarte MÁ, Valiente R, Fanarraga ML. Engineering Sub-Cellular Targeting Strategies to Enhance Safe Cytosolic Silica Particle Dissolution in Cells. Pharmaceutics. 2020; 12(6):487. https://doi.org/10.3390/pharmaceutics12060487

Chicago/Turabian Style

Iturrioz-Rodríguez, Nerea; Correa-Duarte, Miguel Á.; Valiente, Rafael; Fanarraga, Mónica L. 2020. "Engineering Sub-Cellular Targeting Strategies to Enhance Safe Cytosolic Silica Particle Dissolution in Cells" Pharmaceutics 12, no. 6: 487. https://doi.org/10.3390/pharmaceutics12060487

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