上海交通大学学报(医学版)

• 论著(基础研究) • 上一篇    下一篇

载紫杉醇纳米诊疗体的制备及初步应用

马静 1, 2,沈鸣 3,段友容 3,杜联芳 2   

  1. 上海交通大学 1. 附属第一人民医院松江分院超声科,上海 201605;2. 附属第一人民医院超声科,上海 200080;3. 医学院附属仁济医院肿瘤研究所,国家肿瘤及基因研究重点实验室,上海 200023
  • 出版日期:2017-02-28 发布日期:2017-02-28
  • 通讯作者: 杜联芳,电子信箱:du_lf@163.com 。
  • 作者简介:马静(1975—),女,副主任医师,博士;电子信箱:majing0709@163.com。
  • 基金资助:

    国家自然科学基金(81271596, 81171352, 81501483)

Preparation and preliminary application of loading PTX nanoparticles

MA Jing1, 2, SHEN Ming3, DUAN You-rong3, DU Lian-fang2   

  1. 1. Department of Ultrasound, Shanghai Songjiang Central Hospital, Shanghai General Hospital Songjiang Branch, Shanghai Jiao Tong University,Shanghai 201605, China;2.Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China; 3. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200023, China
  • Online:2017-02-28 Published:2017-02-28
  • Supported by:

    National Natural Science Foundation of China, 81271596, 81171352, 81501483

摘要:

目的 ·以生物可降解聚乳酸乙醇酸-甲氧基聚乙二醇(PLGA-mPEG)为骨架,构建包载紫杉醇(PTX)的有机高分子超声纳米诊疗体,初步验证其在胰腺癌体表种植瘤的超声造影显像效果及体外抗肿瘤作用。方法 ·采用复乳法制备载PTX的PLGA-mPEG超声纳米诊疗体(PTX-NPs),并通过设计四因素三水平的正交试验,以包封率和载药量为考查指标,对制备条件进行优化,得出最佳工艺参数。超细微粒粒度/电位分析仪检测所构建的PTX-NPs平均粒径和电位,透射电子显微镜(TEM)检测纳米诊疗体大小、形态、分布、团聚等情况。检测PTX-NPs在体外和裸鼠胰腺癌体表种植瘤的超声造影显像。CCK-8试验检测PTX-NPs的体外抗肿瘤效果。结果 ·成功制备PTX-NPs,包封率和载药率分别为(91.32±3.25)%和(2.666±0.092)%。超声纳米诊疗体的平均粒径为(80.6±3.8)nm,电位为(-13.4±1.5)mv;TEM证实PTX-NPs呈球形、表面光滑、分布均匀、无明显团聚现象。PTX-NPs在体外和胰腺癌体表种植瘤的超声造影显像良好。CCK-8试验结果显示,该纳米诊疗体能显著降低细胞生存率,且同时给予超声照射(US)或超声靶向破坏微泡(UTMD)可进一步降低细胞生存率。结论 · PTX-NPs在胰腺癌体表种植瘤的超声造影显像效果良好;在离体状态下,PTX-NPs具有一定的抗肿瘤治疗效果,且US和UTMD能增强该纳米诊疗体的离体抗肿瘤作用。

关键词: 紫杉醇, 纳米诊疗体, 超声显像, 胰腺癌, 抗肿瘤

Abstract:

Objective · To prepare the nanoparticles encapsulating PTX with organic biodegradable poly (lactic-co-glycolic acid)-monomethoxypoly (ethylene glycol) (PLGA-mPEG) as skeleton, and then to verify its ultrasound contrast enhanced imaging in superficial implantation tumor of pancreatic cancer and its antitumor effect in vitro. Methods · PTX-PLGA-mPEG (PTX-NPs) were prepared by double emulsion method. The preparation conditions were optimized through the design of four factors three levels orthogonal test with entrapment efficiency and loading drug efficiency as examining indexes in order to obtain optimum process parameters. Average particle size and electrical potential of the prepared PTX-NPs were examined by nano particle size and zeta potential analyzer. Size, morphology, distribution, and reunion were detected by transmission electron microscope (TEM). Ultrasound contrast enhanced imaging of PTX-NPs was observed in vitro and in superficial implantation tumor of pancreatic cancer in nude mice. Antitumor effect in vitro of PTX-NPs was detected by CCK-8 test. Results · PTX-NPs were prepared successfully. Entrapment efficiency and loading drug efficiency were (91.32±3.25)% and (2.666±0.092)%, respectively. The average size was (80.6±3.8) nm and the potential was (-13.4±1.5) mv. The morphology of PTX-NPs under TEM was spherical with excellent dispersion and no aggregation. The particles also showed a good image in vitro and in vivo. The result of CCK-8 test demonstrated that PTX-NPs significantly reduced survival rate of pancreatic carcinoma cells, and ultrasound (US) or targeted ultrasound microbubble (UTMD) given at the same time could further decrease the cell survival rate. Conclusion · PTX-NPs are good at ultrasound contrast enhanced imaging in superficial implantation tumor of pancreatic cancer. In vitro PTX-NPs have certain anti-tumor effect, which can be enhanced by US and UTMD.

Key words: PTX, nanoparticles, ultrasound imaging, pancreatic carcinoma, antitumor treatment