Glioblastoma multiforme (GBM) is a fatal central nervous system tumor without effective treatment. Chemotherapeutic agents are mainstays in the treatment of glioblastoma. However, the effectiveness of these is seriously hindered by poor blood–brain‐barrier (BBB) penetrance and tumor targeting, together with short biological half‐life. Improved chemotherapy is thus urgently needed for GBM. Multifunctional nanoparticle delivery systems offer much promise in overcoming current limitations. Accordingly, a multifunctional biomimetic nanomedicine is developed by functionalizing the surface of red blood cell membranes (RBCms) with angiopep‐2 and loading pH‐sensitive nanoparticles (polymer, doxorubicin (Dox), and lexiscan (Lex)) using the functionalized cell membrane to generate the novel nanomedicine, Ang‐RBCm@NM‐(Dox/Lex). The studies toward orthotopic U87MG human glioblastoma tumor‐bearing nude mice show that the Ang‐RBCm@NM‐(Dox/Lex) nanomedicine has much improved blood circulation time, superb BBB penetration, superior tumor accumulation and retention. Moreover, effective suppression of tumor growth and significantly improved medium survival time are also observed after Ang‐RBCm@NM‐(Dox/Lex) treatment. The results show that this biomimetic nanoplatform can serve as a flexible and powerful system for GBM treatment which can be readily adapted for the treatment of other central nervous system (CNS) disorders.

中文翻译：

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通过多功能仿生纳米药物进行有效且有针对性的人类原位胶质母细胞瘤异种移植治疗

多形性胶质母细胞瘤 (GBM) 是一种致命的中枢神经系统肿瘤，目前尚无有效治疗方法。化疗药物是治疗胶质母细胞瘤的主要药物。然而，血脑屏障 (BBB) 外显率和肿瘤靶向性差，以及生物半衰期短，严重阻碍了这些方法的有效性。因此，GBM 迫切需要改进的化学疗法。多功能纳米粒子递送系统在克服当前限制方面提供了很大希望。因此，通过用 angiopep-2 功能化红细胞膜 (RBCms) 的表面并使用功能化的细胞膜加载 pH 敏感纳米粒子（聚合物、多柔比星 (Dox) 和 lexiscan (Lex)）来开发多功能仿生纳米药物生成新型纳米药物 Ang-RBCm@NM-(Dox/Lex)。对原位 U87MG 人胶质母细胞瘤荷瘤裸鼠的研究表明，Ang-RBCm@NM-(Dox/Lex) 纳米药物具有显着改善的血液循环时间、极好的 BBB 渗透、优异的肿瘤积累和保留。此外，在 Ang-RBCm@NM-(Dox/Lex) 处理后，还观察到肿瘤生长的有效抑制和中等存活时间的显着改善。结果表明，这种仿生纳米平台可以作为 GBM 治疗的灵活而强大的系统，可以很容易地适应其他中枢神经系统 (CNS) 疾病的治疗。在 Ang-RBCm@NM-(Dox/Lex) 治疗后，还观察到肿瘤生长的有效抑制和中等存活时间的显着改善。结果表明，这种仿生纳米平台可以作为 GBM 治疗的灵活而强大的系统，可以很容易地适应其他中枢神经系统 (CNS) 疾病的治疗。在 Ang-RBCm@NM-(Dox/Lex) 治疗后，还观察到肿瘤生长的有效抑制和中等存活时间的显着改善。结果表明，这种仿生纳米平台可以作为 GBM 治疗的灵活而强大的系统，可以很容易地适应其他中枢神经系统 (CNS) 疾病的治疗。