Near-Infrared Light-Controlled MicroRNA-21-Loaded Upconversion Nanoparticles to Promote Bone Formation in the Midpalatal Suture

Rapid maxillary expansion (RME) is a common therapy for maxillary transverse deficiency. However, relapses after RME usually occur because of insufficient bone formation. MicroRNA-21 (miR-21) was reported as an important post-transcriptional modulator for osteogenesis. Herein, a photocontrolled miR-21 (PC-miR-21)-loaded nanosystem using upconversion nanoparticles (UCNPs) modified with poly(ether imide) (PEI), i.e., UCNPs@PEI@PC-miR-21, was constructed to promote bone formation in the midpalatal suture. UCNPs@PEI was constructed as the light transducer and delivery carrier. The UCNPs@PEI@PC-miR-21 nanocomplexes have good aqueous dispersibility and biocompatibility. The in vitro cell experiment suggested that UCNPs@PEI could protect PC-miR-21 from biodegradation and release PC-miR-21 into the cytoplasm under near-infrared light (NIR) irradiation. Furthermore, UCNPs@PEI@PC-miR-21 upregulated the expression of the osteogenic key markers, ALP, RUNX2, and COL1A1, at the levels of both genes and proteins. Besides, the results of the in vivo RME mice models further corroborated that photocontrollable UCNPs@PEI@PC-miR-21 accelerated bone formation with upregulating osteogenic markers of ALP, RUNX2, and osteoprotegerin and inducing fewer osteoclasts formation. In conclusion, UCNPs@PEI@PC-miR-21 nanoparticles with a NIR light could facilitate the remote and precise delivery of exogenous miR-21 to the midpalatal suture to promote bone formation during RME. This work represents a cutting-edge approach of gene therapy to promote osteogenesis in the midpalatal suture during RME and provides a frontier scientific basis for later clinical treatment.