Improving glioblastoma therapeutic outcomes via doxorubicin-loaded nanomicelles modified with borneol
Improving glioblastoma therapeutic outcomes via doxorubicin-loaded nanomicelles modified with borneol
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DOI：
10.1016/j.ijpharm.2019.118485
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发表时间：
2019-08-15
影响因子：
5.8
通讯作者：
Gao, Zhonggao
中科院分区：
文献类型：
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作者：
Meng, Lingwei;Chu, Xiaoyang;Gao, Zhonggao
胶质母细胞瘤是一种IV级恶性胶质瘤，具有高复发和转移性，并且面临血脑屏障（BBB）严重阻碍治疗药物的脑进入和疗效的治疗障碍。以前的研究表明，Bo（BO）已被用于增强感兴趣的药物穿透血脑屏障。在这项研究中，建立了一个紫杉醇修饰的纳米胶束给药系统，以促进脑内阿霉素治疗胶质母细胞瘤。本文首次将聚乙二醇分子与DSPE-PEG（2000）-COOH偶联，合成了新型载体DSPE-PEG（2000）-BO，并对其结构进行了表征。以DSPE-PEG（2000）-BO为载体，通过静电作用制备了阿霉素纳米胶束（DOX BO-PMs），并对其理化性质进行了研究。DOX BO-PMs的平均粒径和zeta电位分别为（14.95 ± 0.17）nm和（-1.27 ± 0.06）mV，药物包封率和载药量分别为（95.69 ± 0.49）%和（14.62 ± 0.39）%。DOX BO-PM的药物释放表现出时间和pH依赖性模式。结果表明，DOX BO-PMs显著增强了DOX穿过BBB的转运效率，并且在脑组织中也表现出快速蓄积。体外抗增殖实验结果表明，DOX BO-PMs对胶质母细胞瘤细胞的增殖具有较强的抑制作用。重要的是，体内抗肿瘤结果表明DOX BO-PM显著抑制胶质母细胞瘤的肿瘤生长和转移。结论：DOX BO-PMs可改善胶质母细胞瘤的治疗效果，有望成为阿霉素在胶质母细胞瘤治疗领域的一种有前景的纳米药物候选物。
Glioblastoma is a grade IV malignant glioma with high recurrence and metastasis and faces a therapeutic obstacle that the blood-brain barrier (BBB) severely hinders the brain entry and efficacy of therapeutic drugs. Previous studies suggest that borneol (BO) has been used to enhance interested drugs to penetrate the BBB. In this study, a borneol-modified nanomicelle delivery system was established to facilitate the brain entry of doxorubicin for glioblastoma therapy. Herein, we firstly conjugated borneol molecules with DSPE-PEG(2000)-COOH to synthesize a novel carrier DSPE-PEG(2000)-BO and also characterized its structure. Doxorubicin-loaded nanomicelles (DOX BO-PMs) were prepared using DSPE-PEG(2000)-BO via electrostatic interaction and the physicochemical properties were investigated. The average particle size and zeta potential of DOX BO-PMs were respectively (14.95 +/- 0.17)nm and ( -1.27 +/- 0.06)mV, and the drug encapsulation efficiency and loading capacity in DOX BO-PMs were (95.69 +/- 0.49)% and (14.62 +/- 0.39)%, respectively. The drug release of the DOX BO-PMs exhibited a both time- and pH-dependent pattern. The results demonstrated that DOX BO-PMs significantly enhanced the transport efficiency of DOX across the BBB and also exhibited a quick accumulation in the brain tissues. The in vitro anti-proliferation assay results suggested that DOX BO-PMs exerted a strong inhibitory effect on proliferation of glioblastoma cells. Importantly, in vivo antitumor results demonstrated that DOX BO-PMs significantly inhibited the tumor growth and metastasis of glioblastoma. In conclusion, DOX BO-PMs can improve the glioblastoma therapeutic outcomes and become a promising nanodrug candidate for the application of doxorubicin in the field of glioblastoma therapy.