Bioconjugated Carbon Dots for Delivery of siTnfα to Enhance Chondrogenesis of Mesenchymal Stem Cells by Suppression of Inflammation

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 α (TNFα) plays an important role and may be a potential target. In this study, we investigated the effect of Tnfα 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 TNFα (siTnfα) 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 siTnfα into the MSCs. CD‐SMCC‐siTnfα nanoformula also exhibited considerably high transfection efficiency and nearly no cytotoxicity, which is preferred over commercial polyethyleneimine. Interference of Tnfα by CD‐SMCC‐siTnfα markedly promoted the chondrogenesis of MSCs, as indicated by upregulating cartilage‐specific markers. Furthermore, in vivo exploration indicated that CD‐SMCC‐siTnfα transfected MSCs accelerated cartilage regeneration. In conclusion, this study demonstrated that in combination with the novel CD‐SMCC nanovector, targeting Tnfα may facilitate stem cell‐based therapy of cartilage defects. stem cells translational medicine 2019;8:724&736