Green synthesis of fluorescent carbon nanodots from sage leaves for selective anticancer activity on 2D liver cancer cells and 3D multicellular tumor spheroids

Shadi Sawalha; Samer Abdallah; Amal Barham; Hala Badawi; Zeina Barham; Ahmad Ghareeb; Giuseppe Misia; Silvia Collavini; Alessandro Silvestri; Maurizio Prato; Mohyeddin Assali

doi:10.1039/d3na00269a

Green synthesis of fluorescent carbon nanodots from sage leaves for selective anticancer activity on 2D liver cancer cells and 3D multicellular tumor spheroids

Nanoscale Adv. 2023 Sep 28;5(21):5974-5982. doi: 10.1039/d3na00269a. eCollection 2023 Oct 24.

Authors

Affiliations

¹ Chemical Engineering Program, Faculty of Engineering and Information Technology, An-Najah National University P.O. Box 7 Nablus Palestine sh.sawalha@najah.edu.
² Department of Biology and Biotechnology, Faculty of Science, An-Najah National University P.O. Box 7 Nablus Palestine.
³ Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University P.O. Box 7 Nablus Palestine m.d.assali@najah.edu.
⁴ Department of Chemical and Pharmaceutical Sciences INSTM UdR Trieste, University of Trieste via Licio Giorgieri 1 34127 Trieste Italy.
⁵ Center for Cooperative Research in Biomaterials (CIC BiomaGUNE), Basque Research and Technology Alliance (BRTA) Donostia-San Sebastián 20014 Spain.
⁶ Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice Venezia 30170 Italy.

Abstract

Carbon nanodots, a family of carbon-based nanomaterials, have been synthesized through different methods from various resources, affecting the properties of the resulting product and their application. Herein, carbon nanodots (CNDs) were synthesized with a green and simple hydrothermal method from sage leaves at 200 °C for 6 hours. The obtained CNDs are well dispersed in water with a negative surface charge (ζ-potential = -11 mV) and an average particle size of 3.6 nm. The synthesized CNDs showed concentration-dependent anticancer activity toward liver cancer (Hep3B) cell lines and decreased the viability of the cancer cells to 23% at the highest used concentration (250 μg ml^-1 of CNDs). More interestingly, the cytotoxicity of the CNDs was tested in normal liver cell lines (LX2) revealed that the CNDs at all tested concentrations didn't affect their viability including at the highest concentration showing a viability of 86.7%. The cellular uptake mechanisms of CNDs were investigated and they are thought to be through energy-dependent endocytosis and also through passive diffusion. The main mechanisms of endocytosis were lipid and caveolae-mediated endocytosis. In addition, the CNDs have hindered the formation of 3D spheroids from the Hep3B hepatocellular carcinoma cell line. Hence, it would be concluded that the synthesized CNDs from sage are more highly selective to liver cancer cells than normal ones. The CNDs' cancer-killing ability would be referred to as the production of reactive oxygen species.