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Article

Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis

1
Unidad Asociada Neurodeath, Universidad de Castilla-La Mancha, 02006 Albacete, Spain
2
CIBERNED, Instituto de Salud Carlos III, 28029 Madrid, Spain
3
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, 41012 Sevilla, Spain
4
Instituto de Investigaciones Químicas (IIQ), Consejo Superior de Investigaciones Científicas-Universidad de Sevilla, 41092 Sevilla, Spain, [email protected]
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9306; https://doi.org/10.3390/ijms21239306
Received: 2 November 2020 / Revised: 30 November 2020 / Accepted: 3 December 2020 / Published: 6 December 2020
(This article belongs to the Special Issue Human Immunodeficiency Virus (HIV))
Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane. There is no information about which is the most efficient endocytosis route for high siRNA transfection efficiency. One of the most promising carriers to efficiently deliver siRNA are cyclodextrin derivatives. We have used nanocomplexes composed of siRNA and a β-cyclodextrin derivative, AMC6, with a very high transfection efficiency to selectively knockdown clathrin heavy chain, caveolin 1, and p21 Activated Kinase 1 to specifically block clathrin-mediated, caveolin-mediated and macropinocytosis endocytic pathways. The main objective was to identify whether there is a preferential endocytic pathway associated with high siRNA transfection efficiency. We have found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo. However, blockade of macropinocytosis does not affect AMC6-mediated transfection efficiency, suggesting that macropinocytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytosis. View Full-Text
Keywords: siRNA; β-cyclodextrin; endocytosis; transfection efficiency; micropinocytosis siRNA; β-cyclodextrin; endocytosis; transfection efficiency; micropinocytosis
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MDPI and ACS Style

Manzanares, D.; Pérez-Carrión, M.D.; Jiménez Blanco, J.L.; Ortiz Mellet, C.; García Fernández, J.M.; Ceña, V. Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis. Int. J. Mol. Sci. 2020, 21, 9306. https://doi.org/10.3390/ijms21239306

AMA Style

Manzanares D, Pérez-Carrión MD, Jiménez Blanco JL, Ortiz Mellet C, García Fernández JM, Ceña V. Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis. International Journal of Molecular Sciences. 2020; 21(23):9306. https://doi.org/10.3390/ijms21239306

Chicago/Turabian Style

Manzanares, Darío, María D. Pérez-Carrión, José L. Jiménez Blanco, Carmen Ortiz Mellet, José M. García Fernández, and Valentín Ceña. 2020. "Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis" International Journal of Molecular Sciences 21, no. 23: 9306. https://doi.org/10.3390/ijms21239306

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