Metformin derived carbon dots: Highly biocompatible fluorescent nanomaterials as mitochondrial targeting and blood-brain barrier penetrating biomarkers

• Published in: Journal of colloid and interface science 2021-06, Vol.592, p.485-497
• Main Authors: Kirbas Cilingir, Emel, Seven, Elif S., Zhou, Yiqun, Walters, Brian M., Mintz, Keenan J., Pandey, Raja R., Wikramanayake, Athula H., Chusuei, Charles C., Vanni, Steven, Graham, Regina M., Leblanc, Roger M.
• Format: Article
• Language: English
• Subjects: BBB penetration; Bioimaging; Biomarker; Met-CDs; Mitochondrial and nucleus targeting
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2021.02.058

[Display omitted] •Metformin was used as a precursor to synthesize carbon dots, for the first time.•Met-CDs showed excellent biocompatibility towards both non-tumor and tumor cells.•Met-CDs can penetrate the cell membrane and disperse throughout the cell including the nucleus and mitochondria.•After 1 hour of treatment, Met-CDs tend to localize inside the mitochondria.•Met-CDs can cross the blood–brain barrier without the need of any other ligand on their surface. Carbon dots (CDs) have been intensively studied since their discovery in 2004 because of their unique properties such as low toxicity, excellent biocompatibility, high photoluminescence (PL) and good water dispersibility. In this study metformin derived carbon dots (Met-CDs) were synthesized using a microwave assisted method. Met-CDs were meticulously characterized using ultra-violet spectroscopy (UV–vis), photoluminescence (PL), Fourier Transform Infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), atomic force (AFM) and transmission electron (TEM) microscopies. According to results of cytotoxicity studies, Met-CDs possess low-toxicity and excellent biocompatibility towards both non-tumor and tumor cell lines indicating that Met-CDs are outstanding candidates for living cell bioimaging studies. Furthermore, bioimaging studies have displayed that Met-CDs can penetrate the cell membrane and disperse throughout the cell structure including the nucleus and mitochondria. More specifically, Met-CDs tend to start localizing selectively inside the mitochondria of cancer cells, but not of non-tumor cells after 1 h of incubation. Finally, a zebrafish study confirmed that Met-CDs cross the blood–brain barrier (BBB) without the need of any other ligands. In summary, this study presents synthesis of Met-CDs which feature abilities such as mitochondrial and nucleus localizations along with BBB penetration.