Abstract:
Contrary to the initial belief that myofibroblasts are terminally differentiated cells, myofibroblasts have now been widely recognized as an activation state that is reversible. Therefore, strategies targeting myofibroblast to be a quiescent state may be an effective way for antihypertrophic scar therapy. Graphene quantum dots (GQDs), a novel zero-dimensional and carbon-based nanomaterial, have recently garnered significant interest in nanobiomedicine, owing to their excellent biocompatibility, tunable photoluminescence, and superior physiological stability. Although multiple nanoparticles have been used to alleviate hypertrophic scars, a GQD-based therapy has not been reported. Our in vivo studies showed that GQDs exhibited significant antiscar efficacy, with scar appearance improvement, collagen reduction and rearrangement, and inhibition of myofibroblast overproliferation. Further in vitro experiments revealed that GQDs inhibited α-SMA expression, collagen synthesis, and cell proliferation and migration, inducing myofibroblasts to become quiescent fibroblasts. Mechanistic studies have demonstrated that the effect of GQDs on myofibroblast proliferation blocked cell cycle progression by disrupting the cyclin-CDK-E2F axis. This study suggests that GQDs, which promote myofibroblast-to-fibroblast transition, could be a novel antiscar nanomedicine for the treatment of hypertrophic scars and other types of pathological fibrosis.
摘要:
与最初认为肌成纤维细胞是终末分化细胞的观点相反,肌成纤维细胞现已被广泛认为是可逆的激活状态。因此,针对肌成纤维细胞处于静止状态的策略可能是抗增生性瘢痕治疗的有效方法。石墨烯量子点(GQDs),一种新型的零维和碳基纳米材料,最近在纳米生物医学方面引起了极大的兴趣,由于其优异的生物相容性,可调光致发光,和优越的生理稳定性。尽管多种纳米粒子已被用于减轻肥厚性疤痕,尚未报道基于GQD的治疗。我们的体内研究表明,GQDs表现出显著的抗瘢痕功效,随着疤痕外观的改善,胶原蛋白减少和重排,和抑制肌成纤维细胞过度增殖。进一步的体外实验表明,GQDs抑制α-SMA表达,胶原蛋白合成,细胞增殖和迁移,诱导肌成纤维细胞成为静止的成纤维细胞。机制研究表明,GQD对肌成纤维细胞增殖的影响通过破坏细胞周期蛋白-CDK-E2F轴来阻断细胞周期进程。这项研究表明,GQDs,促进肌成纤维细胞到成纤维细胞的转变,可能是一种新型的抗瘢痕纳米药物,用于治疗增生性瘢痕和其他类型的病理性纤维化。