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（例如神经胶质瘤）的最关键的障碍，神经胶质瘤是最典型的脑瘤类型。为了克服血脑屏障和增强药物穿透能力，我们使用了血管生成肽2修饰的脂质体将三氧化二砷（ATO）输送到血脑屏障，靶向神经胶质瘤。使用乙酸盐梯度法制备了载药量大（7.13±0.72％）的，具有均匀分布的流体动力学直径（96.75±0.57 nm）的Angiopep-2-改性的亚砷酸钙负载脂质体（A2-PEG-LP @ CaAs） ）和包封率（54.30±9.81％）。在酸性肿瘤微环境中，砷被响应性释放，从而发挥抗神经胶质瘤的作用。在体外和体内均研究了A2-PEG-LP @ CaAs的抗神经胶质瘤作用。结果，A2-PEG-LP @ CaAs表现出由脂蛋白受体相关（LRP）受体介导的有效的靶向抗神经胶质瘤作用，在BBB和神经胶质瘤中均过表达。因此，A2-PEG-LP @ CaAs可以极大地促进ATO的抗神经胶质瘤作用，这是一种有希望的神经胶质瘤治疗策略。