In vitro and in vivo toxicological evaluation of carbon quantum dots originating from Spinacia oleracea

Cuicui Fu; Xiaoyun Qin; Jin Zhang; Ting Zhang; Yeqing Song; Jiaqi Yang; Gang Wu; Dan Luo; Nan Jiang; Floris J Bikker

doi:10.1016/j.heliyon.2023.e13422

In vitro and in vivo toxicological evaluation of carbon quantum dots originating from Spinacia oleracea

Heliyon. 2023 Feb 2;9(2):e13422. doi: 10.1016/j.heliyon.2023.e13422. eCollection 2023 Feb.

Authors

Cuicui Fu¹, Xiaoyun Qin², Jin Zhang², Ting Zhang³, Yeqing Song⁴, Jiaqi Yang⁵, Gang Wu^{6

7}, Dan Luo^{8

9}, Nan Jiang⁴, Floris J Bikker¹

Affiliations

¹ Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Amsterdam 1081LA, the Netherlands.
² School of Material and Chemical Engineering, Zhengzhou University of Light Industry, Zhengzhou 450002, China.
³ Laboratory of Biomimetic Nanomaterials, Department of Orthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.
⁴ Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun, South Avenue, Haidian District, Beijing 100081, China.
⁵ Shanxi Medical University School and Hospital of Stomatology& Shanxi Province Key, Laboratory of Oral Diseases Prevention and New Materials, Shanxi 030605, China.
⁶ Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic, Center for Dentistry Amsterdam (ACTA), Amsterdam Movement Science, Vrije Universiteit Amsterdam, Amsterdam 1081LA, the Netherlands.
⁷ Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam 1081LA, the Netherlands.
⁸ CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing 101400, China.
⁹ School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing 100049, China.

Abstract

Food-derived carbon quantum dots (CQDs) can relatively easily be synthesized and chemically manipulated for a broad spectrum of biomedical applications. However, their toxicity may hinder their actual use. Here, Spinacia oleracea-derived CQDs i.e., CQD-1 and CQD-2, were synthesized by means of different shredding methods and followed by a microwave-assisted hydrothermal approach. Subsequently, these CQDs were analyzed in vitro and in an in vivo mice model to test their biocompatibility and potential use as bioimaging agents and for activation of osteogenic differentiation. When comparing CQD-1 and CQD-2, it was found that CQD-1 exhibited 7.6 times higher photoluminescent (PL) emission intensity around 411 nm compared to CQD-2. Besides, it was found that the size distribution of CQD-1 was 2.05 ± 0.08 nm, compared with 2.14 ± 0.04 nm for CQD-2. Upon exposure to human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro, CQD-1 was endocytosed into the cytoplasm and significantly increased the differentiation of hBMSCs up to 10 μg mL^-1 after 7 and 14 days. Apparently, the presence of relatively low doses of CQD-1 showed virtually no toxic or histological effects in the major organs in vivo. In contrast, high doses of CQD-1 (1 mg mL^-1) caused cell death in vitro ranging from 35% on day 1 to 80% on day 3 post-exposure, and activated the apoptotic machinery and increased lymphocyte aggregates in the liver tissue. In conclusion, S. oleracea-derived CQDs have the potential for biomedical applications in bioimaging and activation of stem cells osteogenic differentiation. Therefore, it is postulated that CQD-1 from S. oleracea remains potential prospective material at appropriate doses and specifications.

Keywords: Carbon quantum dots; Fluorescence; Food safety; Spinacia oleracea; Toxicity.