Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. China.
Adv Mater. 2018 Jul;30(30):e1800316. doi: 10.1002/adma.201800316. Epub 2018 Jun 11.
Glioblastoma is a most intractable and high-mortality malignancy because of its extremely low drug accessibility resulting from the blood-brain barrier (BBB). Here, it is reported that angiopep-2-directed and redox-responsive virus-mimicking polymersomes (ANG-PS) (angiopep-2 is a peptide targeting to low-density lipoprotein receptor-related protein-1 (LRP-1)) can efficiently and selectively chaperone saporin (SAP), a highly potent natural protein toxin, to orthotopic human glioblastoma xenografts in nude mice. Unlike chemotherapeutics, free SAP has a low cytotoxicity. SAP-loaded ANG-PS displays, however, a striking antitumor activity (half-maximal inhibitory concentration, IC = 30.2 × 10 m) toward U-87 MG human glioblastoma cells in vitro as well as high BBB transcytosis and glioblastoma accumulation in vivo. The systemic administration of SAP-loaded ANG-PS to U-87 MG orthotopic human-glioblastoma-bearing mice brings about little side effects, effective tumor inhibition, and significantly improved survival rate. The protein toxins chaperoned by LRP-1-targeted virus-mimicking vesicles emerge as a novel and highly promising treatment modality for glioblastoma.
胶质母细胞瘤是一种最棘手和高死亡率的恶性肿瘤，因为其极低的药物可及性，这是由于血脑屏障（BBB）的存在。在这里，据报道，载有血管肽-2（ANG）和氧化还原响应型病毒样聚合物囊泡（ANG-PS）（血管肽-2是一种靶向低密度脂蛋白受体相关蛋白-1（LRP-1）的肽）可以有效地和选择性地将蓖麻毒素（SAP），一种高效的天然蛋白毒素，递送到裸鼠原位人胶质母细胞瘤异种移植瘤中。与化疗药物不同，游离 SAP 的细胞毒性较低。然而，负载 SAP 的 ANG-PS 对 U-87 MG 人胶质母细胞瘤细胞在体外表现出显著的抗肿瘤活性（半最大抑制浓度，IC 50 = 30.2 × 10 m），以及在体内具有高血脑屏障转胞吞作用和胶质母细胞瘤积累。SAP 负载的 ANG-PS 全身给药到 U-87 MG 原位人胶质母细胞瘤荷瘤小鼠中，几乎没有副作用，有效抑制肿瘤，并显著提高了存活率。由 LRP-1 靶向的病毒样囊泡递呈的蛋白毒素为胶质母细胞瘤提供了一种新颖且极具前途的治疗方式。
