Lu Xuanping, Zhou Weiqin, Mao Caiping
Reproductive Medicine Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
J Fluoresc. 2024 Sep 13. doi: 10.1007/s10895-024-03883-7.
Recurrent miscarriage (RM), defined as three or more consecutive spontaneous miscarriages, affects many women of childbearing age. The pathological basis of RM is an imbalance in apoptosis, with the MDM2-p53 pathway playing a crucial role. In this study, we synthesized poly(6-acetoxyl-ε-caprolactone)-graft-(4-amino-benzimidazole) (PCCL-4-ABI) by modifying poly(6-acetoxyl-ε-caprolactone) (PCCL) with 4-amino-benzimidazole (4-ABI). The introduction of carboxyl and 4-ABI groups endowed the PCL backbone with fluorescence, pH responsiveness, and UCST responsiveness. The temperature-dependent release behavior of compound 1-loaded PCCL-4-ABI nanofluorescent materials was attributed to UCST transition. We successfully developed a novel nanofluorescent polymer drug delivery platform, PCCL-4-ABI@1, and evaluated its regulatory effects on p53 and MDM2 in trophoblast cells (HTR-8/SVneo). The results showed that the system loaded with low molecular weight heparin increased MDM2 and decreased p53 expression in a dose-dependent manner, thereby inhibiting trophoblast cell apoptosis. This study developed a biodegradable poly(ε-caprolactone) with UCST behavior, significant for the advancement of thermoresponsive fluorescent nanoparticle systems.
复发性流产（RM）定义为连续三次或更多次自然流产，影响着许多育龄妇女。RM的病理基础是细胞凋亡失衡，其中MDM2-p53通路起着关键作用。在本研究中，我们通过用4-氨基苯并咪唑（4-ABI）修饰聚（6-乙酰氧基-ε-己内酯）（PCCL）合成了聚（6-乙酰氧基-ε-己内酯）-接枝-（4-氨基苯并咪唑）（PCCL-4-ABI）。羧基和4-ABI基团的引入赋予了PCL主链荧光、pH响应性和低临界溶液温度（UCST）响应性。负载化合物1的PCCL-4-ABI纳米荧光材料的温度依赖性释放行为归因于UCST转变。我们成功开发了一种新型纳米荧光聚合物药物递送平台PCCL-4-ABI@1，并评估了其对滋养层细胞（HTR-8/SVneo）中p53和MDM2的调节作用。结果表明，负载低分子量肝素的该系统以剂量依赖性方式增加MDM2并降低p53表达，从而抑制滋养层细胞凋亡。本研究开发了一种具有UCST行为的可生物降解聚（ε-己内酯），这对热响应性荧光纳米颗粒系统的发展具有重要意义。
