Multifunctional magnetite nanoparticles to enable delivery of siRNA for the potential treatment of Alzheimer’s

Autor: Natalia Lopez-Barbosa, Juan G. Garcia, Javier Cifuentes, Lina M. Castro, Felipe Vargas, Carlos Ostos, Gloria P. Cardona-Gomez, Alher Mauricio Hernandez, Juan C. Cruz
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Drug Delivery, Vol 27, Iss 1, Pp 864-875 (2020)
Druh dokumentu: article
ISSN: 1071-7544
1521-0464
10717544
DOI: 10.1080/10717544.2020.1775724
Popis: Therapeutic drugs for Alzheimer’s disease have been extensively studied due to its recurrence and abundance among neurodegenerative diseases. It is thought that the accumulation of amyloid precursor protein (APP) products, a consequence of an up-regulation of the β-site APP-cleaving enzyme 1 (BACE1), is the main triggering mechanism during the early stages of the disease. This study aims to explore the ability of a multifunctional conjugate based on magnetite nanoparticles for the cellular delivery of siRNA against the expression of the BACE1 gene. We immobilized the siRNA strand on PEGylated magnetite nanoparticles and investigated the effects on biocompatibility and efficacy of the conjugation. Similarly, we co-immobilized the translocating protein OmpA on PEGylated nanoparticles to enhance cellular uptake and endosomal escape. BACE1 suppression was statistically significant in HFF-1 cells, without any presence of a cytotoxic effect. The delivery of the nanoconjugate was achieved through endocytosis pathways, where endosome formation was likely escaped due to the proton-sponge effect characteristic of PEGylated nanoparticles or mainly by direct translocation in the case of OmpA/PEGylated nanoparticles.
Databáze: Directory of Open Access Journals
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