Upconverting Carbon Nanodots from Ethylenediaminetetraacetic Acid (EDTA) as Near‐Infrared Activated Phototheranostic Agents

• Published in: Chemistry : a European journal 2019-04, Vol.25 (21), p.5539-5546
• Main Authors: Ortega‐Liebana, M. Carmen, Encabo‐Berzosa, M. Mar, Casanova, Alvaro, Pereboom, M. Desiree, Alda, J. Octavio, Hueso, Jose L., Santamaria, Jesus
• Format: Article
• Language: English
• Subjects: Acetic acid; Activated carbon; Anions; biomarkers; Cancer; carbon nanodots; Chemistry; Cytometry; Cytotoxicity; Edetic acid; Ethylenediaminetetraacetic acids; Fluorescence; Hydrogen peroxide; Infrared imaging; Irradiation; Near infrared radiation; near-infrared irradiation; Optical properties; Photodynamic therapy; phototheranostics; Radiation; reactive oxidative species; Reactive oxygen species; Superoxide; Superoxide anions; Toxicity; Tumor cells
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201806307

This work describes the synthesis of nitrogen‐doped carbon nanodots (CNDs) synthesized from ethylenediaminetetraacetic acid (EDTA) as a precursor and their application as luminescent agents with a dual‐mode theranostic role as near‐infrared (NIR) triggered imaging and photodynamic therapy agents. Interestingly, these fluorescent CNDs are more rapidly and selectively internalized by tumor cells and exhibit very limited cytotoxicity until remotely activated with a NIR illumination source. These CNDs are excellent candidates for phototheranostic purposes, for example, simultaneous imaging and therapy can be carried out on cancer cells by using their luminescent properties and the in situ generation of reactive oxidative species (ROS) upon excitation in the NIR range. In the presence of CNDs, NIR remote activation induces the in vitro killing of U251MG cells. Through the use of flow imaging cytometry, we have been able to successfully map and quantify the different types of cell deaths induced by the presence of intracellular superoxide anions (.O2−) and hydrogen peroxide (H2O2) ROS generated in situ upon NIR irradiation. Multi‐tasking dots: Carbon nanodots obtained from ethylenediaminetetraacetic acid (EDTA) are presented as multifunctional theranostic agents with enhanced response in the NIR biological window. These N‐doped dots exhibit reduced cytotoxicity and a preferential uptake by tumoral cells. Irradiation with a NIR source enables the effective imaging of cells and the simultaneous generation of reactive oxygen species (ROS) able to promote rapid necrosis of cancer cells (see figure).