Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, 710069, China.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China.
Biomater Sci. 2022 Jan 18;10(2):423-434. doi: 10.1039/d1bm01506k.
Glioblastoma multiforme (GBM) is an aggressive and malignant brain tumor with high mortality. The current treatment strategies are still unsatisfactory for this devastating disease. Here, we developed a glucose-functionalized liposome (gLTP) that co-loads temozolomide (TMZ) and pro-apoptotic peptide (PAP) to achieve synergistic efficacy towards GBM. The gLTP can readily penetrate the blood-brain barrier the glucose-GLUT1 pathway and release the TMZ and PAP in the cells. The PAP destroys the mitochondria and subsequently depletes ATP generation, making the GBM cells more sensitive to TMZ-mediated chemotherapy. gLTP exhibits the best anti-tumor effect on the subcutaneous brain tumor model compared to other treatments, including a single drug (TMZ or PAP) liposome and TMZ and PAP physical mixture. On the highly aggressive intracranial tumor model, gLTP can readily penetrate the BBB and efficiently deliver the drugs into the brain tumor, leading to striking improvements in total survival compared to the other treatments. This strategy potentially inspires new attempts to design more effective anti-GBM formulations.
多形性胶质母细胞瘤（GBM）是一种侵袭性和恶性脑肿瘤，死亡率很高。目前的治疗策略对于这种毁灭性疾病仍然不尽如人意。在这里，我们开发了一种葡萄糖功能化脂质体（gLTP），它共载有替莫唑胺（TMZ）和促凋亡肽（PAP），以实现对 GBM 的协同疗效。gLTP 可以很容易地穿透血脑屏障 葡萄糖-GLUT1 途径，并在细胞中释放 TMZ 和 PAP。PAP 破坏线粒体，随后耗尽 ATP 的产生，使 GBM 细胞对 TMZ 介导的化疗更敏感。gLTP 与其他治疗方法（包括单一药物（TMZ 或 PAP）脂质体和 TMZ 和 PAP 物理混合物）相比，在皮下脑肿瘤模型中表现出最佳的抗肿瘤效果。在高度侵袭性的颅内肿瘤模型中，gLTP 可以很容易地穿透 BBB 并将药物有效地递送到脑肿瘤中，与其他治疗方法相比，总生存期显著改善。这种策略可能激发了设计更有效的抗 GBM 制剂的新尝试。
