Innovation Center for Traditional Tibetan Medicine Modernization and Quality Control, Medicine College of Tibet University, Lhasa, China.
University of Tibetan Medicine, Lhasa, China.
Artif Cells Nanomed Biotechnol. 2021 Dec;49(1):596-605. doi: 10.1080/21691401.2020.1814314.
Brain glioma is the most common primary tumour of the central nervous system. Complete surgical removal of the brain glioma is virtually impossible. Chemotherapy is still an important treatment for brain glioma. However, blood-brain barrier (BBB) and vasculogenic mimicry (VM) channels remain two hindrances in regular treatments. Herein, we developed a novel nanoscaled dual targeting daunorubicin plus rofecoxib liposomes which could transport across the BBB, and eliminate brain glioma cells along with the VM channels. The liposomes were modified with two functional materials, and showed round in shape with a diameter about 120 nm. Evaluations were performed on human brain glioma U87MG cells and on intracranial brain glioma-bearing nude mice. The dual targeting liposomes demonstrated a long circulatory effect in the blood system, were able to transport across the BBB, and were accumulated into the brain. The results indicated that the dual targeting daunorubicin plus rofecoxib liposomes could inhibit the brain glioma VM channels and exhibited a significant efficacy in the treatment of intracranial glioma-bearing nude mice. The mechanisms are related to down regulations MMP-2, MMP-9, FAK and HIF-α. Hence, the established dual targeting liposomes could be a potential formulation to treat the brain glioma along with eliminating VM channels.
脑胶质瘤是中枢神经系统最常见的原发性肿瘤。实际上，完全切除脑胶质瘤是不可能的。化疗仍然是脑胶质瘤的重要治疗方法。然而，血脑屏障（BBB）和血管生成拟态（VM）通道仍然是常规治疗的两个障碍。在此，我们开发了一种新型纳米级双重靶向柔红霉素加罗非昔布脂质体，可穿透血脑屏障，并通过 VM 通道消除脑胶质瘤细胞。脂质体用两种功能材料进行修饰，呈圆形，直径约 120nm。在人脑胶质瘤 U87MG 细胞和颅内脑胶质瘤荷瘤裸鼠上进行了评价。双重靶向脂质体在血液系统中表现出长循环效应，能够穿透血脑屏障并在脑内蓄积。结果表明，双重靶向柔红霉素加罗非昔布脂质体可抑制脑胶质瘤 VM 通道，并在治疗颅内脑胶质瘤荷瘤裸鼠中显示出显著疗效。其机制与下调 MMP-2、MMP-9、FAK 和 HIF-α有关。因此，所建立的双重靶向脂质体可能是一种治疗脑胶质瘤并消除 VM 通道的潜在制剂。
