TY - JOUR
T1 - Ascorbic Acid-PEI Carbon Dots with Osteogenic Effects as miR-2861 Carriers to Effectively Enhance Bone Regeneration
AU - Bu, Wenhuan
AU - Xu, Xiaowei
AU - Wang, Zilin
AU - Jin, Nianqiang
AU - Liu, Lili
AU - Liu, Jie
AU - Zhu, Shoujun
AU - Zhang, Kai
AU - Jelinek, Raz
AU - Zhou, Ding
AU - Sun, Hongchen
AU - Yang, Bai
N1 - Publisher Copyright:
©
PY - 2020/11/11
Y1 - 2020/11/11
N2 - Nucleic acid transfer has shown significant potential in the treatment of bone damage because of its long lasting local effect and lower cost. Nonviral vectors, such as nanomaterials, with higher biocompatibility are increasedly applied in the study of bone defect repair. Carbon dots with various reactive groups on the surface not only provide a unique surface to carry therapeutic genes, but also some carbon dots have been reported to promote osteogenic differentiation. The bone regeneration effect of carbon dots in vivo, however, is rarely investigated. MiR-2861 has revealed osteogenic differentiation effects. In the current study, we created ascorbic acid-PEI carbon dots (CD), which were able to carry miR-2861, by the microwave-assisted pyrolysis method. Results demonstrated that CD had excellent fluorescence stability leading to good fluorescence imaging in vitro and in vivo. CD was efficiently internalized into bone marrow stromal cells (BMSCs) through the clathrin-mediated endocytosis pathway and distributed in the mitochondria, endoplasmic reticulum, lysosome, and nucleus. Results from alkaline phosphatase staining, alizarin red staining, and reverse transcription real-time PCR (RT-QPCR) showed that our CD indeed had osteogenic effects in vitro. Flow cytometry data indicated that CD could efficiently deliver miR-2861 into BMSCs in vitro, and CD carrying miR-2861 (CD@miR) had the strongest osteogenic effects. Analyses of hematology, serum biochemistry, and histology showed that CD and CD@miR did not have cytotoxicity and had higher biocompatibility in vivo. Most interestingly, CD and miR-2861 in the CD@miR could act synergistically to promote osteogenic differentiation in vitro and new bone regeneration in vivo remarkably. Our results clearly indicate that the osteogenic CD delivering osteogenic therapeutic gene, miR-2861, can obtain much stronger bone regeneration ability, suggesting that our CD has great potential in future clinical application.
AB - Nucleic acid transfer has shown significant potential in the treatment of bone damage because of its long lasting local effect and lower cost. Nonviral vectors, such as nanomaterials, with higher biocompatibility are increasedly applied in the study of bone defect repair. Carbon dots with various reactive groups on the surface not only provide a unique surface to carry therapeutic genes, but also some carbon dots have been reported to promote osteogenic differentiation. The bone regeneration effect of carbon dots in vivo, however, is rarely investigated. MiR-2861 has revealed osteogenic differentiation effects. In the current study, we created ascorbic acid-PEI carbon dots (CD), which were able to carry miR-2861, by the microwave-assisted pyrolysis method. Results demonstrated that CD had excellent fluorescence stability leading to good fluorescence imaging in vitro and in vivo. CD was efficiently internalized into bone marrow stromal cells (BMSCs) through the clathrin-mediated endocytosis pathway and distributed in the mitochondria, endoplasmic reticulum, lysosome, and nucleus. Results from alkaline phosphatase staining, alizarin red staining, and reverse transcription real-time PCR (RT-QPCR) showed that our CD indeed had osteogenic effects in vitro. Flow cytometry data indicated that CD could efficiently deliver miR-2861 into BMSCs in vitro, and CD carrying miR-2861 (CD@miR) had the strongest osteogenic effects. Analyses of hematology, serum biochemistry, and histology showed that CD and CD@miR did not have cytotoxicity and had higher biocompatibility in vivo. Most interestingly, CD and miR-2861 in the CD@miR could act synergistically to promote osteogenic differentiation in vitro and new bone regeneration in vivo remarkably. Our results clearly indicate that the osteogenic CD delivering osteogenic therapeutic gene, miR-2861, can obtain much stronger bone regeneration ability, suggesting that our CD has great potential in future clinical application.
KW - Biocompatibility
KW - Bone marrow stromal cells
KW - Bone regeneration
KW - Carbon dots
KW - MiR-2861
UR - http://www.scopus.com/inward/record.url?scp=85096080056&partnerID=8YFLogxK
U2 - 10.1021/acsami.0c15425
DO - 10.1021/acsami.0c15425
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C2 - 33121247
AN - SCOPUS:85096080056
VL - 12
SP - 50287
EP - 50302
JO - ACS applied materials & interfaces
JF - ACS applied materials & interfaces
SN - 1944-8244
IS - 45
ER -