研究领域：纳米技术 药剂学 伤口愈合 生物医学工程

关键字：空心聚多巴胺纳米颗粒 RL-QN15 肽 促再生疗法 皮肤伤口 角质形成细胞 巨噬细胞 细胞因子 动物模型 全层皮肤损伤 口腔溃疡 皮肤烫伤

背景：尽管随着治疗方法和制剂的增加，皮肤伤口的治疗已取得显著进展，但现有的干预手段仍无法满足当前的临床需求。因此，开发新型促再生疗法仍十分迫切。纳米材料和多肽凭借其独特的特性，为促再生制剂的开发提供了新的线索，但仍需进一步深入研究和探索。结果：在本研究中，我们成功合成了空心聚多巴胺（HPDA）纳米颗粒，并成功制备了负载RL-QN15（一种具有显著促愈合活性的两栖动物源多肽）的HPDA纳米颗粒（HPDAlR）。我们评估了HPDA纳米颗粒和HPDAlR的理化特性、生物分布及清除情况，并测定了HPDA对RL-QN15的负载效率以及RL-QN15从HPDAlR中的缓释速率。研究结果显示，HPDA纳米颗粒和HPDAlR对角质形成细胞、巨噬细胞及小鼠均无明显毒性，且HPDA纳米颗粒在体内和体外均未表现出促愈合活性。有趣的是，HPDAlR显著增强了RL-QN15加速角质形成细胞划痕愈合的能力，并能选择性调节巨噬细胞释放与愈合相关的细胞因子。更重要的是，通过在小鼠全层皮肤损伤模型和大鼠口腔溃疡模型上进行评估，与游离的RL-QN15相比，HPDAlR的促再生效力分别显著提高了50倍和10倍。此外，HPDAlR还增强了多肽RL-QN15对小鼠皮肤烫伤和猪全层损伤伤口的促愈合效率。结论：HPDA显著增强了RL-QN15在体内和体外的促再生效力，因此HPDAlR在皮肤伤口愈合治疗药物的开发中展现出巨大潜力。Background Although the treatments of skin wounds have greatly improved with the increase in therapeutic methods and agents, available interventions still cannot meet the current clinical needs. Therefore, the development of new pro-regenerative therapies remains urgent. Owing to their unique characteristics, both nanomaterials and peptides have provided novel clues for the development of pro-regenerative agents, however, more efforts were still be awaited and anticipated.Results In the current research, Hollow polydopamine (HPDA) nanoparticles were synthesized and HPDA nanoparticles loading with RL-QN15 (HPDAlR) that was an amphibian-derived peptide with obvious prohealing activities were prepared successfully. The characterization, biodistribution and clearance of both HPDA nanoparticles and HPDAlR were evaluated, the loading efficiency of HPDA against RL-QN15 and the slow-releasing rate of RL-QN15 from HPDAlR were also determined. Our results showed that both HPDA nanoparticles and HPDAlR exerted no obvious toxicity against keratinocyte, macrophage and mice, and HPDA nanoparticles showed no prohealing potency in vivo and in vitro. Interestingly, HPDAlR significantly enhanced the ability of RL-QN15 to accelerate the healing of scratch of keratinocytes and selectively modulate the release of healing-involved cytokines from macrophages. More importantly, in comparison with RL-QN15, by evaluating on animal models of full-thickness injured skin wounds in mice and oral ulcers in rats, HPDAlR showed significant increasing in the pro-regenerative potency of 50 and 10 times, respectively. Moreover, HPDAlR also enhanced the prohealing efficiency of peptide RL-QN15 against skin scald in mice and full-thickness injured wounds in swine.Conclusion sHPDA obviously enhanced the pro-regenerative potency of RL-QN15 in vitro and in vivo, hence HPDAlR exhibited great potential in the development of therapeutics for skin wound healing.