2. Academic Validation
  3. Ascorbic Acid-PEI Carbon Dots with Osteogenic Effects as miR-2861 Carriers to Effectively Enhance Bone Regeneration

Ascorbic Acid-PEI Carbon Dots with Osteogenic Effects as miR-2861 Carriers to Effectively Enhance Bone Regeneration

  • ACS Appl Mater Interfaces. 2020 Nov 11;12(45):50287-50302. doi: 10.1021/acsami.0c15425.
Wenhuan Bu 1 2 3 4,  Xiaowei Xu 5,  Zilin Wang 6,  Nianqiang Jin 1,  Lili Liu 6,  Jie Liu 7,  Shoujun Zhu 8,  Kai Zhang 8,  Raz Jelinek 9,  Ding Zhou 10,  Hongchen Sun 1 3,  Bai Yang 8
Affiliations

Affiliations

  • 1 Liaoning Provincial Key Laboratory of Oral Diseases, School of Stomatology, China Medical University, Shenyang 110001, China.
  • 2 Department of Dental Materials, School of Stomatology, China Medical University, Shenyang 110001, China.
  • 3 Department of Oral Pathology, School of Stomatology, China Medical University, Shenyang 110001, China.
  • 4 Department of Center Laboratory, School of Stomatology, China Medical University, Shenyang 110001, China.
  • 5 Department of Periodontology, School and Hospital of Stomatology, Jilin University, Changchun 130021, China.
  • 6 Department of Oral Pathology, School and Hospital of Stomatology, Jilin University, Changchun 130021, China.
  • 7 Department of Oral and Maxillofacial Surgery, School of Stomatology, Wuhan University, Wuhan 430000, China.
  • 8 State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
  • 9 Department of Chemistry, Ilse Katz Institute for Nanotechnology, Ben Gurion University of the Negev, Beer Sheva 8410501, Israel.
  • 10 State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.
PMID: 33121247 DOI: 10.1021/acsami.0c15425
Abstract

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.

Keywords

biocompatibility; bone marrow stromal cells; bone regeneration; carbon dots; miR-2861.

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