Pep-1引导的基聚多巴胺载药替莫唑胺纳米颗粒用于胶质母细胞瘤化疗及光热双重治疗  

Pep-1-guided PDA loaded temozolomide nanoparticles for chemotherapy and photothermal double combination therapy of glioblastoma

作　　者：吴浩 刘琦[3] 魏民 马强 李育平 张恒柱 WU Hao;LIU Qi;WEI Min;MA Qiang;LI Yuping;ZHANG Hengzhu(Graduate School of Dalian Medical University,Liaoning Dalian 116044,China;Department of Neurosurgery,Clinical MedicalCollege,Yangzhou University,Jiangsu Yangzhou 225001,China;Department of Neurosurgery,The First Hospital of Yulin SuideBranch,Shaanxi Yulin 718000,China)

机构地区：[1]大连医科大学研究生院,辽宁大连116044 [2]扬州大学临床医学院神经外科,江苏扬州225001 [3]榆林市第一医院绥德院区神经外科,陕西榆林718000

出　　处：《现代肿瘤医学》2023年第15期2789-2798,共10页Journal of Modern Oncology

基　　金：国家自然科学基金(编号:82172603)。

摘　　要：目的:构建由Pep-1引导的基聚多巴胺(PDA)载药替莫唑胺(TMZ)的纳米颗粒(NPs)用于胶质母细胞瘤的化疗及光热的双重治疗。方法:利用PDA的邻苯二酚、氨基、羧基等活性基团及超强的黏附性与TMZ和Pep-1的羰基、氨基及巯基发生席夫碱反应及自组装,得到Pep-1@PDA-TMZ NPs;使用动态光散射及透射电子显微镜对其尺寸、电荷及形貌进行表征;采用傅里叶红外光谱及紫外光谱对其药物的负载及组装进行分析;使用水、胎牛血清对其稳定性进行考察;采用近红外热成像仪验证其光热转换效能;并考察TMZ的释放情况。通过细胞实验验证Pep-1@PDA NPs的生物相容性、细胞摄取情况及Pep-1@PDA-TMZ NPs对于U87和C6细胞的抑制率。结果:制备的Pep-1@PDA-TMZ NPs形态较规则,呈球形,尺寸约140 nm,载药量约50%;细胞内吞成像表明U87和C6细胞对Pep-1@PDA-TMZ NPs的吞噬量高于PDA-TMZ NPs;在808 nm激光的照射下,Pep-1@PDA-TMZ NPs对U87和C6细胞的抑制率分别为90.81%和82.29%(P<0.05)。结论:纳米递药系统Pep-1@PDA-TMZ NPs的载药率较高、穿透力较强、生物相容性及靶向性较好,能够提供化疗和光疗为一体的双重治疗作用。Objective:To construct Pep-1-guided polydopamine-loaded temozolomide nanoparticles for chemotherapy and photothermal double combination therapy of glioblastoma.Methods:The Schiff base reaction and self-assembly of the active groups of PDA,such as catechol,amino group and carboxyl group,with the carbonyl group,amino group and sulfhydryl group of TMZ and Pep-1,were carried out to obtain Pep-1@PDA-TMZ NPs.The size,charge and morphology of these groups were characterized by dynamic light scattering and transmission electron microscopy.Fourier infrared spectrum and ultraviolet spectrum were used to analyze the loading and assembly of the drug.Water and fetal bovine serum were used to investigate its stability.The near infrared thermal imager was used to verify the photothermal conversion efficiency.And examine the release of TMZ.Cell experiments were conducted to verify the biocompatibility and uptake of Pep-1@PDA NPs and the inhibition rate of Pep-1@PDA-TMZ NPs on U87 and C6 cells.Results:The prepared Pep-1@PDA-TMZ NPs was spherical with a size of about 140 nm and a drug loading of about 50%.Endocytosis imaging showed that the phagocytosis of Pep-1@PDA-TMZ NPs by U87 and C6 cells was higher than PDA-TMZ NPs.Under 808 nm laser irradiation,Pep-1@PDA-TMZ NPs inhibited U87 and C6 cells by 90.81%and 82.29%,respectively(P<0.05).Conclusion:The nano drug delivery system Pep-1@PDA-TMZ NPs has high drug loading rate,strong penetration,good biocompatibility and targeting,and can provide chemotherapy and phototherapy as one of the dual therapeutic effects,which is expected to be gradually transformed into clinical research.

关 键 词：替莫唑胺 聚多巴胺 细胞穿膜肽-1 胶质母细胞瘤 纳米递药系统 联合治疗 

分 类 号：R730.261[医药卫生—肿瘤]