Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, and School of Science, Harbin Institute of Technology, Shenzhen 518055, China.
Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Harbin Institute of Technology, Shenzhen 518055, China.
Nanoscale. 2023 Jul 6;15(26):10904-10938. doi: 10.1039/d3nr01667f.
Glioblastoma (GBM) treatment is still a big clinical challenge because of its highly malignant, invasive, and lethal characteristics. After treatment with the conventional therapeutic paradigm of surgery combined with radio- and chemotherapy, patients bearing GBMs generally exhibit a poor prognosis, with high mortality and a high disability rate. The main reason is the existence of the formidable blood-brain barrier (BBB), aggressive growth, and the infiltration nature of GBMs. Especially, the BBB suppresses the delivery of imaging and therapeutic agents to lesion sites, and thus this leads to difficulties in achieving a timely diagnosis and treatment. Recent studies have demonstrated that extracellular vesicles (EVs) exhibit favorable merits including good biocompatibility, a strong drug loading capacity, long circulation time, good BBB crossing efficiency, specific targeting to lesion sites, and high efficiency in the delivery of a variety of cargos for GBM therapy. Importantly, EVs inherit physiological and pathological molecules from the source cells, which are ideal biomarkers for molecularly tracking the malignant progression of GBMs. Herein, we start by introducing the pathophysiology and physiology of GBMs, followed by presenting the biological functions of EVs in GBMs with a special focus on their role as biomarkers for GBM diagnosis and as messengers in the modulation of the GBM microenvironment. Furthermore, we provide an update on the recent progress of using EVs in biology, functionality, and isolation applications. More importantly, we systematically summarize the most recent advances of EV-based carriers for GBM therapy by delivering different drugs including gene/RNA-based drugs, chemotherapy drugs, imaging agents, and combinatory drugs. Lastly, we point out the challenges and prospects of future research on EVs for diagnosing and treating GBMs. We hope this review will stimulate interest from researchers with different backgrounds and expedite the progress of GBM treatment paradigms.
胶质母细胞瘤（GBM）的治疗仍然是一个巨大的临床挑战，因为它具有高度恶性、侵袭性和致命性的特点。在接受手术联合放化疗的常规治疗模式治疗后，携带 GBM 的患者通常预后较差，死亡率和残疾率较高。主要原因是存在强大的血脑屏障（BBB）、侵袭性生长和 GBM 的浸润特性。特别是，BBB 抑制了成像和治疗剂递送到病变部位，因此导致难以及时诊断和治疗。最近的研究表明，细胞外囊泡（EVs）具有良好的生物相容性、强大的药物载药能力、长循环时间、良好的 BBB 穿透效率、对病变部位的特异性靶向以及高效传递各种载药用于 GBM 治疗等优点。重要的是，EVs 从源细胞继承生理和病理分子，是分子跟踪 GBM 恶性进展的理想生物标志物。在这里，我们首先介绍 GBM 的病理生理学和生理学，然后介绍 EVs 在 GBM 中的生物学功能，特别关注它们作为 GBM 诊断的生物标志物和作为调节 GBM 微环境的信使的作用。此外，我们提供了关于 EV 在生物学、功能和分离应用方面的最新进展的更新。更重要的是，我们系统地总结了基于 EV 的载体在 GBM 治疗中传递不同药物（包括基因/RNA 药物、化疗药物、成像剂和组合药物）的最新进展。最后，我们指出了基于 EV 用于诊断和治疗 GBM 的未来研究的挑战和前景。我们希望这篇综述能激发不同背景的研究人员的兴趣，并加速 GBM 治疗模式的进展。
