Leveraging selective knockdown of Sost gene by polyethyleneimine-siRNA-chitosan reduced gold nanoparticles to promote osteogenesis in MC3T3-E1 & MEF cells

Aim: Osteoporosis is a systemic skeletal disorder characterized by reduced osteoblast differentiation, predominantly by overexpression of the Sost gene. A layer-by-layer approach enabled encapsulation of Sost siRNA to enhance the short half-life and poor transfection capacity of siRNA. Materials & methods: Polyethyleneimine and siRNA on chitosan-coated gold nanoparticles (PEI/siRNA/Cs-AuNPs) were engineered using chitosan-reduced gold nanoparticles. They were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared and gel-mobility assays. Detailed in vitro experiments, gene silencing and western blots were performed. Results: A total of 80% knockdown of the target sclerostin protein was observed by PEI/siRNA/Cs-AuNPs, q-PCR showed threefold downregulation of the Sost gene. Osteogenic markers RunX2 and Alp were significantly upregulated. Conclusion: We report a safe, biocompatible nanotherapeutic strategy to enhance siRNA protection and subsequent silencing to augment bone formation.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

Nanomedicine (London, England) - 19(2024), 10 vom: 19. Apr., Seite 895-914

Sprache:

Englisch

Beteiligte Personen:

Niveria, Karishma [VerfasserIn]
ZafarYab, Mohammad [VerfasserIn]
Biswas, Largee [VerfasserIn]
Mahtab, Asiya [VerfasserIn]
Verma, Anita Kamra [VerfasserIn]

Links:

Volltext

Themen:

7440-57-5
9002-98-6
9012-76-4
Adaptor Proteins, Signal Transducing
Chitosan
Gene silencing
Gold
Gold–chitosan nanoparticles
Journal Article
Osteogenic biomarkers
Osteoporosis
Polyethyleneimine
RNA, Small Interfering
RT-PCR
Research Support, Non-U.S. Gov't
Sost protein, mouse
Sost siRNA

Anmerkungen:

Date Completed 29.03.2024

Date Revised 22.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.2217/nnm-2023-0325

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370204646