Multifunctional exosome-mimetics for targeted anti-glioblastoma therapy by manipulating protein corona

• DOI: 10.1186/s12951-021-01153-3
• Publication Date: 2021-12-06T11:05:59Z
• Authors: Jun-Yong Wu; Yong-Jiang Li; Jiemin Wang; Xiong-Bin Hu; Si Huang; Shilin Luo; Da-Xiong Xiang
• Keywords: 0301 basic medicine; Cell Survival; Antineoplastic Agents; Docetaxel; Exosomes; Blood–brain barrier; Mice; 03 medical and health sciences; Drug Delivery Systems; Biomimetic Materials; Cell Line, Tumor; Medical technology; Animals; Humans; R855-855.5; Exosome-mimetics; Brain Neoplasms; Research; 3. Good health; Blood-Brain Barrier; Drug delivery; Protein Corona; Glioblastoma; TP248.13-248.65; Biotechnology

AbstractTargeted drug delivery to the glioblastoma (GBM) overcoming blood–brain barrier (BBB) has been challenging. Exosomes are promising vehicles for brain tumor drug delivery, but the production and purification hinder its application for nanomedicine. Besides, the formation of protein corona (PC) may affect the behaviour of nanocarriers. Here, multifunctional exosomes-mimetics (EM) are developed and decorated with angiopep-2 (Ang) for enhancing GBM drug delivery by manipulating PC. Docetaxel (DTX)-loaded EM with Ang modification (DTX@Ang-EM) show less absorption of serum proteins and phagocytosis by macrophages. Ang-EM show enhanced BBB penetration ability and targeting ability to the GBM. Ang-EM-mediated delivery increase the concentration of DTX in the tumor area. The multifunctional DTX@Ang-EM exhibits significant inhibition effects on orthotopic GBM growth with reduced side effects of the chemotherapeutic. Findings from this study indicate that the developed DTX@Ang-EM provide a new strategy for targeted brain drug delivery and GBM therapy. Graphical abstract