上海交通大学学报(医学版) ›› 2019, Vol. 39 ›› Issue (4): 347-.doi: 10.3969/j.issn.1674-8115.2019.04.003

• 论著·基础研究 • 上一篇    下一篇

基于光诱导的粒径可变阿霉素纳米递送系统

来星,方超   

  1. 上海交通大学基础医学院药理学与化学生物学系,上海 200025
  • 出版日期:2019-04-28 发布日期:2019-05-23
  • 通讯作者: 方超,电子信箱:fangchao32@sjtu.edu.cn。
  • 作者简介:来星(1994—),女,硕士生;电子信箱: lx438687459@163.com。

Light-induced size-switchable nanosystem for doxorubicin delivery

LAI Xing, FANG Chao   

  1. Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University College of Basic Medical Sciences, Shanghai 200025, China
  • Online:2019-04-28 Published:2019-05-23

摘要: 目的 ·制备在近红外光诱导下实现粒径可变(大变小)的阿霉素( doxorubicin,DOX)纳米递送系统,并考察其光促粒径转换性能及细胞毒性。方法 ·通过滴加法合成载 DOX的聚乙二醇 –聚乳酸 [poly(ethylene glycol)-polylactide,PEG-PLA]纳米粒,采用薄膜水化法将 PEG-PLA-DOX包载入脂质体( liposome,LP)内水腔,并在 LP双分子层间加入光敏剂维替泊芬( verteporfin,VP),合成对近红外光敏感的纳米粒( PEG-PLA-DOX@LP)。利用透射电子显微镜观察各步骤纳米粒形态结构;动态光散射激光粒度仪检测各阶段纳米粒的粒径;评估纳米粒的载药性能和光诱导下的纳米粒尺寸可变行为;考察纳米粒的稳定性及光诱导粒径变化对小鼠黑色素瘤 B16F10细胞活力的影响。结果 ·成功合成了 PEG-PLA-DOX@LP光敏感纳米粒,其粒径为( 194.83±5.70)nm,Zeta表面电势为(-1.43±0.32)mV,DOX载药量 2.82%,VP载药量 1.16%;光照前 LP结构完整,光照后可明显看到粒径为( 37.42±8.67)nm的 PEG-PLA-DOX从 LP中释放;载药纳米粒尺寸显著缩小,产生更有效杀伤肿瘤细胞的作用。结论 ·构建的新型 DOX纳米递送系统可在近红外光诱导下,使药物粒径快速由大变小,增强对肿瘤细胞的杀伤作用。

关键词: 近红外光, 阿霉素, 纳米粒, 粒径可变

Abstract:

Objective · To engineer a light-induced size-switchable (large to small) nanosystem for doxorubicin (DOX) delivery and characterize its light-induced size change and cytotoxicity. Methods · The poly(ethylene glycol)-polylactide nanoparticles loading DOX (PEG-PLA-DOX) were fabricated with the dropwise addition method. Then the nanoparticles were encapsulated into the inner cavity of liposome (LP), and a photosensitizer (verteporfin, VP) was loaded in the bilayers of the LP to engineer the near-infrared light-sensitive core-shell nanoparticles (PEG-PLA-DOX@LP). The morphology of the nanoparticles was observed under a transmission electron microscope. Dynamic light scattering was used to examine the particle size at each stage. The size-switchable property of the nanoparticles and its influence on viability of murine melanoma B16F10 cells under near-infrared light were evaluated. The stability of the nanoparticles was also investigated. Results · PEG-PLA-DOX@LP, the light-sensitive nanoparticles, were successfully developed. The nanoparticles had a particle size of (194.83±5.70) nm and Zeta potential of (-1.43±0.32) mV. The drug loading was 2.82% for DOX, and 1.16% for VP. The small-sized PEG-PLA-DOX [(37.42±8.67) nm]was quickly released the nanoparticles upon light for enhanced toxicity to B16F10 murine melanoma cells. Conclusion · The particle size of the novel DOX delivery nanosystem rapidly changes large size to small size upon the irradiation of near-infrared light, and thus the cytotoxic effect on tumor cells can be enhanced. [Key words]near-infrared light; doxorubicin; nanoparticle; size-switchable[National Natural Science Foundation of China, 81773274; Foundation of Shanghai Local High Level University (First-class Discipline–Pharmacy) ]。

Key words: near-infrared light, doxorubicin, nanoparticle, size-switchable[National Natural Science Foundation of China, 81773274, Foundation of Shanghai Local High Level University (First-class Discipline&, ndash, Pharmacy) ]。

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