Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, P. R. China.
Adv Healthc Mater. 2021 May;10(9):e2002200. doi: 10.1002/adhm.202002200. Epub 2021 Feb 28.
Gliomas remain difficult to treat because of their metastatic and recurrent nature and the existence of the blood-brain barrier (BBB), which impedes drug delivery. Microglia, the resident macrophages in the CNS, can be recruited by gliomas and can penetrate the tumor. In this study, microglia (BV2 cells) are used as transport vectors to deliver paclitaxel for the treatment of glioma. To avoid paclitaxel toxicity in microglia, liposomes are first employed to isolate the drug from BV2 cells. Dipalmitoyl phosphatidylserine (DPPS), as an "eat me" signal, is doped into liposomes to amplify their phagocytosis by microglia. This study demonstrates that engineered microglia can cross the BBB, independently migrate toward gliomas, and transfer cargo to glioma cells. Of note, extracellular vesicles and tunneling nanotubes are found to offer unique modes of cargo transportation between microglia and glioma cells. In vivo, the engineered drug-loaded microglia has a high ability to target the brain, penetrate glioma, and suppress tumor progression, supporting the notion that the use of engineered microglia is a potential strategy for the treatment of glioma. These findings present new opportunities for exploration into the use of microglia as transport vectors to deliver therapeutic agents through specific membrane nanotubes and vesicles.
由于其转移性和复发性以及血脑屏障 (BBB) 的存在，神经胶质瘤仍然难以治疗，这阻碍了药物的输送。小胶质细胞是中枢神经系统中的常驻巨噬细胞，可以被神经胶质瘤募集，并穿透肿瘤。在这项研究中，小胶质细胞（BV2 细胞）被用作输送载体，输送紫杉醇治疗神经胶质瘤。为了避免小胶质细胞中的紫杉醇毒性，首先使用脂质体将药物与 BV2 细胞隔离。二棕榈酰磷脂酰丝氨酸 (DPPS) 作为“吃我”信号被掺杂到脂质体中，以增强小胶质细胞对其的吞噬作用。本研究表明，工程化的小胶质细胞可以穿过血脑屏障，独立地向神经胶质瘤迁移，并将货物转移到神经胶质瘤细胞。值得注意的是，细胞外囊泡和隧道纳米管为小胶质细胞和神经胶质瘤细胞之间的货物运输提供了独特的方式。在体内，载药的工程化小胶质细胞具有靶向大脑、穿透神经胶质瘤和抑制肿瘤进展的高能力，支持使用工程化小胶质细胞作为治疗神经胶质瘤的潜在策略的观点。这些发现为探索使用小胶质细胞作为输送载体通过特定的膜纳米管和囊泡输送治疗剂提供了新的机会。
