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Monocyte-mediated chemotherapy drug delivery in glioblastoma
Chao Wang1,2, Ke Li3, Tongfei Li1
1Department of Pharmacology, School of Basic Medicine, Wuhan University, Donghu Avenue No.185, Wuhan 430072, China.
Aim:
To mechanistically prove the concept of monocyte-mediated nano drug delivery in glioblastoma (GBM).
Results:
nano-doxorubicin-loaded monocytes (Nano-DOX-MC) were viable, able to cross an artificial endothelial barrier and capable of infiltrating GBM spheroids and releasing drug therein. GBM cells stimulated unloading of Nano-DOX-MC and took up the unloaded drug and released damage-associated molecular patterns. In mice with orthotopic GBM xenografts, Nano-DOX-MC resulted in much improved tumor drug delivery efficacy and damage-associated molecular patterns emission. Mechanistically, Nano-DOX was found sequestered in the lysosomal compartment and to induce autophagy, which may underlie MC's tolerance to Nano-DOX. Lysosomal exocytosis was found involved in the discharging mechanism of intracellular Nano-DOX.
Conclusion:
Nano-DOX can be effectively delivered by MC in GBM and induce cancer cell damage.
