还原响应的白蛋白纳米颗粒负载甲氨蝶呤用于抗肿瘤治疗

材料导报

2019, Vol. 33

Issue (Z2): 547-552

高分子与聚合物基复合材料

还原响应的白蛋白纳米颗粒负载甲氨蝶呤用于抗肿瘤治疗

王怀基, 董海青

同济大学医学院生物医学工程与纳米科学研究院,上海 200092

Reductive-responsive Albumin Nanoparticle Loading Methotrexate for Anti-cancer Therapy

WANG Huaiji, DONG Haiqing

The Institute for Biomedical Engineering & Nano Science, School of Medicine, Tongji University, Shanghai 200092

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摘要本研究通过小分子调控牛血清白蛋白分子中巯基暴露,构建一种基于二硫键自组装的白蛋白纳米给药系统。通过负载小分子叶酸类似物甲氨蝶呤(MTX),从而制备出粒径均一、形貌规整、稳定的纳米药物。该纳米药物在280 nm以及395 nm处有显著的紫外吸收峰,表明MTX成功地负载到蛋白纳米颗粒上。还原性分子二硫苏糖醇(DTT)可打断颗粒的二硫键交联网络,诱导颗粒解离以进一步释放MTX。除此之外,体外实验表明该纳米药物可以高效杀伤肿瘤细胞,诱导细胞凋亡。该纳米颗粒也具备良好的稳定性,全1 640培养基条件刺激下,5 d内颗粒尺寸基本不会发生变化。该颗粒还具有较好的生物相容性,几乎不会导致红细胞溶血。实验结果还表明,蛋白纳米颗粒(BSA NP)及负载MTX的颗粒(BSA-MTX)可以通过内吞进入肿瘤细胞。BSA-MTX可以有效抑制小鼠肿瘤的生长,显著提升肿瘤的治疗效果。该二硫键交联的白蛋白纳米药物递送系统在肿瘤治疗以及临床转化方面具有较好的前景。

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关键词: 二硫键自组装白蛋白纳米颗粒还原响应肿瘤治疗

Abstract: We constructed a self-assembly albumin nanoparticle-based drug delivery system based on disulfide bond by mediating the thiol exposure of bovine serum albumin (BSA). BSA nanoparticle (BSA NP) loaded with methotrexate (MTX) was synthesized successfully which exhibited good size distribution, morphology and high zeta potential. MTX loaded BSA NP (BSA-MTX) had two absorption peaks at 280 nm and 395 nm, respectively, which proved that MTX was loaded into BSA NP successfully. The disulfide cross-linking nets within the reductive-responsive nanoparticle could be disrupted by dithiothreitol (DTT), a reductive molecule, so as to induce the dissociation of BSA-MTX to release MTX. The size of BSA-MTX experienced small change incubated with RPMI 1640 containing 10% FBS within 5 days. Moreover, BSA-MTX exhibited stronger toxicity towards B16F10 cancer cells and induced cancer cells apoptosis efficiently. Besides, BSA-MTX was biocompatible which would not cause the hemolysis in vitro. Meanwhile, BSA-MTX along with BSA NP could be endocytosed by cancer cell, an indicative of the loaded MTX hardly affecting the cell uptake efficiency of BSA NP. BSA-MTX was able to inhibit the tumor growth of the mice and significantly improve the therapeutic effect effectively. The novel albumin nanoparticle-based drug delivery system provides a new approach for cancer therapy.

Key words: disulfide bond self-assembly albumin nanoparticle reductive-responsive cancer therapy

出版日期: 2019-11-25 发布日期: 2019-11-25

ZTFLH:

TB324

基金资助: 国家自然科学基金面上项目(31771090)

通讯作者: inano_donghq@tongji.edu.cn

作者简介: 王怀基,男,同济大学医学院硕士研究生,主要研究方向为生物医用高分子及超分子自组装在纳米医学及纳米技术领域的应用。
董海青,理学博士,同济大学医学院生物医学工程与纳米科学研究院副研究员,博士研究生导师,2009年毕业于武汉大学化学与分子科学学院。主要研究方向为生物医用高分子及超分子自组装在纳米医学及纳米技术领域的应用,以及免疫细胞载体在肿瘤靶向及治疗的应用研究。

引用本文:

王怀基, 董海青. 还原响应的白蛋白纳米颗粒负载甲氨蝶呤用于抗肿瘤治疗[J]. 材料导报, 2019, 33(Z2): 547-552.
WANG Huaiji, DONG Haiqing. Reductive-responsive Albumin Nanoparticle Loading Methotrexate for Anti-cancer Therapy. Materials Reports, 2019, 33(Z2): 547-552.

链接本文:

http://www.mater-rep.com/CN/ 或 http://www.mater-rep.com/CN/Y2019/V33/IZ2/547

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