Hyaluronic acid mediated biomineralization of multifunctional ceria nanocomposites as ROS scavengers and tumor photodynamic therapy agents

Currently, there is great interest in developing ceria-based nanomaterials for biomedical applications. However, the development of nontoxic and eco-friendly processes for ceria nanomaterial synthesis remains a major challenge. Herein, hyaluronic acid (HA)-directed synthesis was reported under facile and mild reaction conditions for the first time. The obtained HA@ ceria nanoquantum dots (HA@ CQDs) exhibited efficient protective effects against damage induced by a series of in vitro reactive oxygen species (ROS)-generating models. In vivo, HA@ CQDs chiefly distributed in the liver with no obvious toxicity and protected hepatocytes from damage caused by ROS. Furthermore, HA@ CQDs-Ce-6 was employed to assess cellular uptake. Considerably, significantly enhanced cellular uptake of HA@ CQDs-Ce-6 was observed in HeLa cells due to the strong receptor-binding affinity of HA to CD44. More importantly, the in vitro photodynamic therapy (PDT) results showed that HA@ CQDs-Ce-6/H2O2 exhibits an excellent tumor PDT effect assisted by H2O2 due to the dramatically increased cellular uptake of Ce-6 and the enhancement of the O-2 level. Taken together, our research emphasizes a green route to synthesize stabilized and dispersed HA@ CQDs and recognize these compounds as ROS scavengers and therapeutic carriers to target tumors for PDT treatment.