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

Abstract

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 <i>in vitro</i> 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 <i>in vivo</i> 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.