Theranostic Photoactive Composite Particles from Photoactive Graphitic Carbon Nitride (g-C3N4) and Hyaluronic Acid–Gd/Fe(III) Microparticles

Graphitic carbon nitrides (g-C3N4) are well-known fluorescent nanosheets that are photoactive under the UV–visible light range and could generate reactive oxygen species (ROS) upon appropriate light exposure. Therefore, these materials are generally favored in diagnostic applications for bioimaging and light-activated treatments simultaneously, e.g., theranostic applications in cancer treatments. Here, the natural polymer, hyaluronic acid (HA), was physically crosslinked with trivalent metal ions such as Gd(III) or Fe(III) ions in the presence of boron (B)- or sulfur (S)-doped graphitic carbon nitride (g-C3N4) nanosheets to attain spherical light-sensitive g-C3N4@HA-M(III) (M: G(III) or Fe(III) ions) composite microparticles. The g-C3N4@HA-M(III) particles were in the 0.5–20 μm size range, which is injectable for possible intravenous administration. No significant toxicity was determined for g-C3N4@HA-Gd(III) particles up to 500 μg/mL concentration on L929 fibroblast cells; for example, g-C3N4@HA-Fe(III) particles could be used in vivo applications safely up to 100 μg/mL concentration with no toxicity. The g-C3N4-based materials exhibited strong fluorescence at λex 380 nm, and S-doped g-C3N4@HA-Gd(III) particles provided the highest emission intensity for possible cell imaging applications as a diagnostic tool material. Especially, S-doped g-C3N4@HA-M(III) particles delivered photoinduced anticancer activity on SKMEL 30 skin cancer cells after 30 min of UV-A treatment at 6.88 mW/cm2 irradiance and 12.38 J/cm fluence via the reactive oxygen species (ROS) production capability. In addition to the targeting ability of HA-M(III) particles, the photoinduced anticancer activity of g-C3N4@HA-M(III) particles, e.g., on SKMEL 30 melanoma cells, offer great alternatives to toxic chemo- or radiotherapy. Furthermore, HA-Gd(III)-based particles show the highest signal intensity with better proton relaxation times and the highest proton longitudinal relaxivity. Overall, HA-Gd/Fe(III) particles with heteroatom-doped g-C3N4 revealed excellent assets with enhanced MRI capabilities in addition to specific targeted cancer treatments and photoinduced therapy for multifaceted theranostic applications.