Engineered Microglia Potentiate the Action of Drugs against Glioma Through Extracellular Vesicles and Tunneling Nanotubes

Abstract

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.

The Mechanism Study of Common Flavonoids on Antiglioma Based on Network Pharmacology and Molecular Docking

“…DL indicates the potential of a compound to be developed into a therapeutic drug with respect to its physical and chemical properties. BBB impedes drug distribution between blood and brain [ 8 ], which is a very important parameter in the treatment of glioma. In general, one compound is considered permeable across the BBB when its BBB permeability is larger than −0.30.…”

Microglia and Brain Macrophages as Drivers of Glioma Progression

“…This is particularly interesting because tumour-associated microglia and macrophages often contribute to the failure of oncolytic virotherapy by preventing an efficient intratumoral viral distribution [ 212 ]. Another study has suggested that engineered microglia can be used to potentiate the action of drugs against glioma [ 213 ]. In the latter study extracellular vesicles and tunnelling nanotubes were employed.…”

The role of tumor neogenesis pipelines in tumor progression and their therapeutic potential

“…Engineered microglia loaded with paclitaxel were generated. These engineered microglia establish intercellular communication specifically to glioma cells and deliver drugs through TNTs 112 …”