Near-infrared light-controlled kartogenin delivery of multifunctional Prussian blue nanocomposites for cartilage defect repair

Articular cartilage injury repair remains a challenge for clinicians and researchers. Mesenchymal stem cells (MSCs) have multiple differentiation potentials and can be induced to differentiate into the chondrogenic lineage for cartilage defect repair; however, the insufficient capacity of chondrogenic differentiation and excess reactive oxygen species (ROS)-mediated oxidative stress, which always lead to differentiation into hypertrophic chondrocytes, still need to be resolved. Accordingly, kartogenin (KGN), which can promote chondrogenic differentiation of MSCs, has shown promise in promoting infected cartilage repair. However, realizing controllable release to prolong its action time and avoid hypertrophic differentiation is critical. We herein developed a mesoporous Prussian blue nanoparticle (mPB)-based near-infrared (NIR) light-responsive controlled nanosystem. KGN was encapsulated in temperature-stimulated responsive phase change materials (PCMs), which were used as excellent gating materials (KGN-PCM@mPBs). In addition, the mPBs could efficiently scavenge ROS by their enzyme-like antioxidative activities. Our study demonstrates that the nanocomposites could efficiently promote chondrogenic differentiation and successfully inhibit the hypertrophic differentiation of MSCs. By intra-articular injection of KGN-PCM@mPBs and NIR-triggered precisely controlled release, satisfactory cartilage repair effects can be achieved in a rat chondral defect model. Thus, this constructed NIR-mediated KGN-PCM@mPB nanoplatform may represent an effective cartilage repair strategy with satisfactory biosafety in clinical applications.