Nitrogen-doped Hollow Carbon Nanospheres as a Delivery Platform Enhance the Availability and Therapeutic Efficacy of Curcumin in Inflammatory Bone Defect Repair

Abstract

Curcumin, a bioactive substance isolated from turmeric root (Curcuma longa), positively regulates the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). However, curcumin suffers from low bioavailability due to its poor water solubility and tendency to agglomerate (high surface energy). Moreover, curcumin's poor stability and susceptibility to decomposition (photosensitivity) further limit its applications. Herein, we synthesized a surface-oxidized nitrogen-doped hollow carbon nanosphere (N-HCSO) drug carrier with an intact inner cavity (~210 nm) and microporous-mesoporous composite carbon layer structure. N-HCSO enhanced the dispersibility of curcumin (preventing self-agglomeration), resulting in a decrease in curcumin particle size and an increase in water solubility. Due to the ultraviolet and visible light absorption properties of N-HCSO, it effectively protected curcumin, thereby indirectly preventing its photodegradation under intense ultraviolet-visible light irradiation, and the photodegradation rate of curcumin in the N-HCSO-Cur system was only about 12.3%. The resulting complex was designated N-HCSO-Cur and applied to treat inflammatory bone defects. Cell proliferation, osteogenic behaviors, and oxidative stress tests revealed that lipopolysaccharide (LPS) treatment of BMSC reduced alkaline phosphatase activity, matrix mineralization, and osteogenic differentiation gene expression but increased reactive oxygen species (ROS) levels. The N-HCSO-Cur presented remarkable protective effects against LPS-induced biochemical changes. In vivo, LPS inhibited bone remodeling and increased heme oxygenase-1 levels in cranial bone defects. N-HCSO-Cur effectively increased bone remodeling caused by LPS. Overall, the N-HCSO-Cur protective effects of lowering ROS levels and improving BMSC osteogenesis make it a promising novel therapeutic strategy for inflammatory bone defects. Its drug carrier, N-HCSO, is also suitable for loading other poorly soluble drugs.