基于T细胞膜修饰的基因递送系统介导脑胶质瘤低温光热治疗研究

Study on Gene Delivery System Mediated by T Cell Membrane Modification for Low-Temperature Photothermal Therapy of Glioma

脑胶质瘤是中枢神经系统最为常见的恶性肿瘤,其在低温光热治疗时面临着热休克蛋白的抵抗和血脑屏障的阻碍等难题。基于此,该研究将T细胞膜修饰于搭载光热剂和HSP90-siRNA的载体表面而合成新型的基因递送系统aT@FVNPs,以期实现脑胶质瘤的低温光热治疗。通过纳米粒度分析仪、紫外−可见光谱仪、荧光光谱仪等测定载体的基本性能,以小鼠内皮细胞Bend.3、脑胶质瘤细胞GL261为研究对象,测定aT@FVNPs穿透内皮细胞性能、敲低HSP90和体外杀伤肿瘤细胞的能力。结果显示aT@FVNPs更易透过内皮细胞屏障,并通过敲低HSP90而在低温光热条件下诱导更强的脑胶质瘤细胞杀伤效果。此外,通过小鼠原位脑胶质瘤模型,进一步评价aT@FVNPs体内脑胶质瘤靶向潜能,显示相较于FVNPs组,其表现出更强的脑胶质瘤部位富集能力;并且在激光处理下,aT@FVNPs组表现出更为明显的病理性坏死,诱导细胞凋亡。总之,aT@FVNPs能够跨越血脑屏障而靶向至脑胶质瘤部位,并通过抑制热休克蛋白表达以实现在低温光热条件下有效杀伤肿瘤细胞的目的。

Gliomas are the most common malignant tumors of the central nervous system and face challenges such as resistance from heat shock proteins and obstacles posed by the blood-brain barrier during lowtemperature photothermal therapy.In this study,a novel gene delivery system,aT@FVNPs,is synthesized by modifying T cell membranes with photothermal agents and HSP90-siRNA on the surface of carriers.This system aims to achieve effective low-temperature photothermal therapy for gliomas.The basic properties of the carriers were determined using a nanoparticle size analyzer,UV-visible spectrophotometer,and fluorescence spectrometer.The performance of aT@FVNPs in penetrating endothelial cells and the ability to knock down HSP90 and kill tumor cells in vitro were assessed using mouse endothelial cells(Bend.3)and glioma cells(GL261).The results showed that aT@FVNPs more readily crossed the endothelial cell barrier and induced stronger glioma cell killing under low-temperature photothermal conditions due to HSP90 knockdown.Additionally,using a mouse orthotopic glioma model,the in vivo targeting potential of aT@FVNPs was further evaluated,demonstrating a stronger accumulation at the glioma site compared to the FVNPs group.With laser irradiation,aT@FVNPs group showed more obvious pathological necrosis and induced cell apoptosis.In summary,aT@FVNPs can cross the blood-brain barrier and target glioma sites,effectively killing tumor cells under low-temperature photothermal conditions by inhibiting heat shock protein expression.