International Journal of Nanomedicine (Jul 2022)
TAT&RGD Peptide-Modified Naringin-Loaded Lipid Nanoparticles Promote the Osteogenic Differentiation of Human Dental Pulp Stem Cells
Abstract
Chun-Yan Zheng,1,* Xiao-Yang Chu,2,* Chun-Yan Gao,1 Hua-Ying Hu,3 Xin He,1 Xu Chen,1 Kai Yang,4 Dong-Liang Zhang1 1Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, Beijing, People’s Republic of China; 2Department of Stomatology, Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Birth Defects Prevention and Control Technology Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Prenatal Diagnosis Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong-Liang Zhang, Department of Orthodontics, Beijing Stomatological Hospital, Capital Medical University School of Stomatology, Capital Medical University, 11 Xilahutong Road, Beijing, 100040, People’s Republic of China, Email [email protected]: Naringin is a naturally occurring flavanone that promotes osteogenesis. Owing to the high lipophilicity, poor in vivo bioavailability, and extensive metabolic alteration upon administration, the clinical efficacy of naringin is understudied. Additionally, information on the molecular mechanism by which it promotes osteogenesis is limited.Methods: In this study, we prepared TAT & RGD peptide-modified naringin-loaded nanoparticles (TAT-RGD-NAR-NPs), evaluated their potency on the osteogenic differentiation of human dental pulp stem cells (hDPSCs), and studied its mechanism of action through metabolomic analysis.Results: The particle size and zeta potential of TAT-RGD-NAR-NPs were 160.70± 2.05 mm and – 20.77± 0.47mV, respectively. The result of cell uptake assay showed that TAT-RGD-NAR-NPs could effectively enter hDPSCs. TAT-RGD-NAR-NPs had a more significant effect on cell proliferation and osteogenic differentiation promotion. Furthermore, in metabolomic analysis, naringin particles showed a strong influence on the glycerophospholipid metabolism pathway of hDPSCs. Specifically, it upregulated the expression of PLA2G3 and PLA2G1B (two isozymes of phospholipase A2, PLA2), increased the biosynthesis of lysophosphatidic acid (LPA).Conclusion: These results suggested that TAT-RGD-NPs might be used for transporting naringin to hDPSCs for modulating stem cell osteogenic differentiation. The metabolomic analysis was used for the first time to elucidate the mechanism by which naringin promotes hDPSCs osteogenesis by upregulating PLA2G3 and PLA2G1B.Keywords: nanoparticles, TAT, RGD, hDPSCs, osteogenic differentiation
