载砷酸钙的 Angiopep-2 修饰脂质体用于靶向和 pH 响应递送来进行抗神经胶质瘤治疗。
Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy.
机构信息
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Libraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
出版信息
Biochem Biophys Res Commun. 2021 Apr 30;551:14-20. doi: 10.1016/j.bbrc.2021.02.138. Epub 2021 Mar 11.
The blood-brain barrier (BBB) is the most critical obstacle in the treatment of central nervous system disorders, such as glioma, the most typical type of brain tumor. To overcome the BBB and enhance drug-penetration abilities, we used angiopep-2-modified liposomes to deliver arsenic trioxide (ATO) across the BBB, targeting the glioma. Angiopep-2-modified calcium arsenite-loaded liposomes (A2-PEG-LP@CaAs), with uniformly distributed hydrodynamic diameter (96.75 ± 0.57 nm), were prepared using the acetate gradient method with high drug-loading capacity (7.13 ± 0.72%) and entrapment efficiency (54.30 ± 9.81%). In the acid tumor microenvironment, arsenic was responsively released, thereby exerting an anti-glioma effect. The anti-glioma effect of A2-PEG-LP@CaAs was investigated both in vitro and in vivo. As a result, A2-PEG-LP@CaAs exhibited a potent, targeted anti-glioma effect mediated by the lipoprotein receptor-related (LRP) receptor, which is overexpressed in both the BBB and glioma. Therefore, A2-PEG-LP@CaAs could dramatically promote the anti-glioma effect of ATO, as a promising strategy for glioma therapy.
血脑屏障（BBB）是治疗中枢神经系统疾病（如脑肿瘤中最典型的类型——神经胶质瘤）的最关键障碍。为了克服 BBB 并增强药物渗透能力，我们使用了载三氧化二砷（ATO）的靶向神经胶质瘤的脑靶向肽修饰的脂质体来递药。采用醋酸梯度法制备了 Angiopep-2 修饰的亚砷酸钙负载脂质体（A2-PEG-LP@CaAs），其具有均一的水动力学直径（96.75±0.57nm），载药率（7.13±0.72%）和包封率（54.30±0.98%）高。在酸性肿瘤微环境中，砷能响应释放，从而发挥抗神经胶质瘤作用。在体外和体内研究了 A2-PEG-LP@CaAs 的抗神经胶质瘤作用。结果表明，A2-PEG-LP@CaAs 通过在 BBB 和神经胶质瘤中过度表达的脂蛋白受体相关（LRP）受体，发挥靶向抗神经胶质瘤作用。因此，A2-PEG-LP@CaAs 可以显著增强 ATO 的抗神经胶质瘤作用，为神经胶质瘤的治疗提供了一种很有前途的策略。
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