Excess curcumin causes cytotoxicity of its nanoconjugate with nanoceria

Curcumin is a natural bioactive substance with promising biomedical applications. However, the low solubility and stability of curcumin significantly limit its potential use. The development of nanoformulations of curcumin makes it possible to circumvent the above limitations. Cerium dioxide (CeO₂, NDC) nanoparticles are a promising platform for curcumin binding. They are able to absorb curcumin on their surface, providing increased bioavailability and bioaccumulation. Moreover, NDC have unique enzyme-like properties that can be used for targeted delivery and controlled release of curcumin. Meanwhile, the potential cytotoxicity of such nanoformulations remains poorly understood. In this work, we synthesized the NDC-curcumin nanoconjugate and investigated the effect of excess curcumin on the cytotoxicity of this nanoformulation. Curcumin has been shown to bind to the surface of nanoparticles, forming a colloidally stable nanoconjugate. At the same time, excess curcumin formed a separate nanoscale fraction, which caused the statistically significant cytotoxicity of the nanoconjugate in relation to human keratinocytes (HaCaT), mesenchymal stem cells (hMSc) and fibroblasts (HF). These cell lines represent the cells that form skin, mucous membranes, and connective tissue, with which curcumin nanoformulations can interact through various methods of administration. IC₅₀ values of curcumin and NDC-curcumin were 400 and 482 μM for HaCaT, 193 and 211 μM for hMSc, 266 and 304 μM for HF, respectively, after 72 h of coincubation. Consequently, NDC provided an increased biocompatibility of curcumin. Application of a rational design of curcumin nanoformulations can help to overcome possible limitations of its practical use due to its toxicity, enhancing its bioactivity.