Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, China.
Department of Implant Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cell Prolif. 2022 Sep;55(9):e13279. doi: 10.1111/cpr.13279. Epub 2022 Jul 9.
Peptide-based therapeutics are natural candidates to desirable wound healing. However, enzymatic surroundings largely limit its stability and bioavailability. Here, we developed a tetrahedral framework nucleic acids(tFNA)-based peptide delivery system, that is, p@tFNAs, to address deficiencies of healing peptide stability and intracellular delivery in diabetic wound healing.
AGEs (advanced glycation end products) were used to treat endothelial cell to simulate cell injury in diabetic microenvironment. The effects and related mechanisms of p@tFNAs on endothelial cell proliferation, migration, angiogenesis and ROS (reactive oxygen species) production have been comprehensively studied. The wound healing model in diabetic mice was photographically and histologically investigated in vivo.
Efficient delivery of healing peptide by the framework(tFNA) was verified. p@tFNAs helped overcome the angiogenic obstacles induced by AGEs via ERK1/2 phosphorylation. In the meantime, p@tFNA exhibited its antioxidative property to achieve ROS balance. As a result, p@tFNA improved angiogenesis and diabetic wound healing in vitro and in vivo.
Our findings demonstrate that p@tFNA could be a novel therapeutic strategy for diabetic wound healing. Moreover, a new method for intracellular delivery of peptides was also constructed.
基于肽的治疗剂是理想的伤口愈合的天然候选物。然而，酶环境在很大程度上限制了其稳定性和生物利用度。在这里，我们开发了一种基于四面体框架核酸（tFNA）的肽递药系统，即 p@tFNAs，以解决糖尿病伤口愈合中治疗肽稳定性和细胞内递药的缺陷。
使用 AGEs（晚期糖基化终产物）处理内皮细胞以模拟糖尿病微环境中的细胞损伤。全面研究了 p@tFNAs 对内皮细胞增殖、迁移、血管生成和 ROS（活性氧）生成的影响及其相关机制。体内通过拍照和组织学研究了糖尿病小鼠的伤口愈合模型。
通过框架（tFNA）实现了治疗肽的高效递药。p@tFNAs 通过 ERK1/2 磷酸化帮助克服 AGEs 诱导的血管生成障碍。同时，p@tFNA 表现出抗氧化特性以实现 ROS 平衡。结果，p@tFNA 改善了体外和体内的血管生成和糖尿病伤口愈合。
我们的研究结果表明，p@tFNA 可能是治疗糖尿病伤口愈合的一种新的治疗策略。此外，还构建了一种新的肽细胞内递药方法。
