Sustained intra-cellular siRNA release from poly(L-arginine) multilayered nanoparticles for prolonged gene silencing.
Expert Opin Drug Deliv
; : 1-10, 2024 Sep 22.
Article
em En
| MEDLINE
| ID: mdl-39290161
ABSTRACT
BACKGROUND:
Sustained siRNA release from nanocarriers is difficult to achieve inside the cell after entry typically, all nanocarriers exhibit burst release of the cargo into the cytoplasm. RESEARCH DESIGN ANDMETHODS:
Layer-by-layer (LbL) nanoparticles (NPs) can be constructed so that they escape endosomes intact, and subsequently exhibit sustained release of the cargo. Our work quantifies intra-cellular siRNA release from multilayered NPs, evaluates mechanism behind the sustained release, and optimizes the duration of release.RESULTS:
Intra-cellular studies showed that NPs developed with four layers of poly-L-arginine, alternated with three layers of siRNA layers, were able to elicit effective and prolonged SPARC knockdown activity over 21 days with a single-dose treatment. For the first time, we have quantified the amounts of released siRNA in the cytoplasm and the amount of siRNA remaining inside the NPs at each timepoint. Furthermore, we have correlated the amount of released siRNA within cells by LbL NPs to the cellular knockdown efficiency of multilayered delivery system.CONCLUSIONS:
This methodology may provide an excellent screening tool for assessing the duration of gene silencing by various nanocarrier formulations.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article