(411i) Heteroatom Doped Graphitic Carbon Nitride (H@g-C3N4) and Carbon Dots (CDs) Embedded Hyaluronic Acid-Gd/Fe(III) Microgels As Photoactivable Theragnostic Materials

Graphitic carbon nitride (g-C₃N₄) and carbon dots (CDs) are well-known photoactive fluorescence nanomaterials capable of generating reactive oxygen species (ROS) upon exposure to UV-visible light. Therefore, these materials are generally favored in theragnostic (diagnosis and treatment) applications via bioimaging and light activation in the treatments of cancers. In this study, heteroatom-doped g-C₃N₄ and CDs as H@g-C₃N₄ and H@CDs were prepared employing sulfur (S), nitrogen (N), boron (B), and phosphorus (P) as heteroatoms to improve the theragnostic effects of these nanomaterials. Furthermore, hyaluronic acid (HA) as cancer cell targeting ability was crosslinked with Gd(III) and Fe(III) ions (M(III)) in the presence of these H@g-C₃N₄ or H@CDs to prepare H@g-C₃N₄/CDs embedded HA-M(III) composite particles as photosensitive materials. These composite particles are in the injectable size range (submicron and micrometer sizes) and showed high fluorescent emission intensity upon excitation at 320 nm. The potential use of H@g-C₃N₄/CDs embedded HA-M(III) composite particles for diagnostic applications via fluorescent imaging and MRI enhancers as well as cancer cell treatments by photoinduced therapy were investigated in vitro. All these materials are biocompatible up to 1000 mg/mL concentration on healthy L929 fibroblast cells as well as non-hemolytic and no clotting effects on blood cells. Furthermore, the cell penetration ability of H@g-C₃N₄/CDs embedded HA-Gd/Fe(III) composite particles was demonstrated via fluorescence microscope images to show the cell imaging properties of the composite microgels. The photoinduced anticancer ability of the H@g-C₃N₄/CDs embedded HA-M(III) composite particles on SKMEL 30 melanoma cells as theragnostic materials were also investigated under UV-light treatment and the corresponding results were compared with the daylight. It was shown that the toxicity of Gd(III) and Fe(III) ions, commonly used in Magnetic Resonance Imaging (MRI) as contrast-enhancing agents was circumvented by the presence of HA that also provided a high-water uptake ability, great biocompatibility, and cancer-targeting ability. The prepared H@g-C₃N₄/CDs embedded HA-M(III) composite particles were found to be excellent contrast enhancers in MRI which was determined by 1H NMR relaxometry measurements and clinical MRI scanners.

Acknowledgments: This work is supported by the Ministry of Health of The Republic of Türkiye (TUSEB-33379).