Bioconjugated Carbon Dots for Delivery of siTnf? to Enhance Chondrogenesis of Mesenchymal Stem Cells by Suppression of Inflammation.

ABSTRACT: Although a promising strategy, the mesenchymal stem cell (MSC)-based therapy of cartilage defects is sometimes accompanied with chronic inflammation during the remodeling status, which may hinder cartilage regeneration. During this process, the inflammatory cytokine tumor necrosis factor ? (TNF?) plays an important role and may be a potential target. In this study, we investigated the effect of Tnf? RNA interference by introducing a functional and highly safe carbon dot (CD)-SMCC nanovector synthesized by bioconjugation of CDs with a protein crosslinker, sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo-SMCC), as the vehicle of the silenced TNF? (siTnf?) on chondrogenesis of MSCs. The results showed that CD-SMCC displayed intense fluorescence with well-dispersed and positively charged properties, which favored effective binding and delivering of siTnf? into the MSCs. CD-SMCC-siTnf? nanoformula also exhibited considerably high transfection efficiency and nearly no cytotoxicity, which is preferred over commercial polyethyleneimine. Interference of Tnf? by CD-SMCC-siTnf? markedly promoted the chondrogenesis of MSCs, as indicated by upregulating cartilage-specific markers. Furthermore, in vivo exploration indicated that CD-SMCC-siTnf? transfected MSCs accelerated cartilage regeneration. In conclusion, this study demonstrated that in combination with the novel CD-SMCC nanovector, targeting Tnf? may facilitate stem cell-based therapy of cartilage defects. Stem Cells Translational Medicine 2019;8:724&736.

SUBMITTER: Liu J 

PROVIDER: S-EPMC6591550 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature