Gd(III) and Fe(III) ion crosslinked hyaluronic acid microgels composites embedding hetero atom doped carbon quantum dots render photodynamic therapy with improved bioimaging capability

In this study, we report the development of multifunctional CQ-dot@HA-Gd/Fe(III) microgels that can be readily simultaneously used in fluorescence/MR dual-mode imaging and photodynamic therapy as theragnostic agents. Nitrogen (N-) and sulfur (S-) heteroatom-doped carbon quantum dots (CQ-dot) were prepared in one step microwave treatment within 3 min as a fluorescence and photoinduced antipathogenic nanomaterial. The N/Sdoped CQ-dots were spherical shaped and < 50 nm via TEM images and showed high fluorescence intensity with 420 nm emission wavelength at maximum lambda(ex):350 nm. The N/S-doped CQ-dots were embedded into ionically crosslinked hyaluronic acid (HA) microgels, employing trivalent metal ions Gd(III) or Fe(III) ions. The prepared CQ-dot@HA-Gd/Fe(III) microgels <5 mm size range are injectable for possible intravenous administration and possess high fluorescent properties. The isoelectric point (IEP) of CQ-dot@HA-Gd and CQ-dot@HA-Fe (III) microgels was determined as pH 1.45. The CQ-dot@HA-Gd/Fe(III) microgels exhibit excellent hemocompatibility without causing noticeable hemolysis and blood clotting at concentrations up to 500 mg/mL. Furthermore, the toxicity of CQ-dot@HA-Gd/Fe(III) microgels on L929 fibroblast cells was found as 100 mg/mL concentration and provide brilliant cell imaging under DAPI filter without any fluorescence dye. Also, the CQdot@HA-Gd/Fe(III) microgel suspension afforded great MRI contrast enhancement ability. Photoinduced anticancer activity was observed for CQ-dot@HA-Gd/Fe(III) microgels even at 50 mg/mL against SK-MEL 30 melanoma cells under UV-A light treatment for 30 min. In addition, high reactive oxygen species (ROS) generation was obtained for the pathogenic bacteria cells by light-sensitive CQ-dot@HA-Gd/Fe(III) microgels upon 30 min UV-A light treatment that triggered the destruction of the Staphylococcus aureus (ATCC 6538).