Active Targeting of Orthotopic Glioma Using Biomimetic Liposomes Co-loaded Elemene and Cabazitaxel Modified By Transferritin

Abstract

Efficient chemotherapy for glioma demands a nanocarrier that can overcome the blood-brain barrier (BBB) and then target the tumor location. Elemene (ELE) and cabazitaxel (CTX) liposomes are prepared by conjugating liposomes with transferrin (Tf) and embedding the cell membrane proteins of RG2 glioma into liposomes (active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP), which are demonstrated resultful in infiltrating the BBB and targeting glioma, respectively. Tf-ELE/CTX@BLIP is highly stable, displaying a prominent peculiarity of homologous targeting and of immune evasion in vitro, and a 5.83-fold intake rate when versus classical liposome (ELE/CTX@LIP). The result of bioluminescence imaging revealed enhanced drugs accumulation in the brain and increased tumor penetration of Tf-ELE/CTX@BLIP in orthotopic glioma model nude mice. In vivo studies demonstrated that the anti-tumor effect of the Tf-ELE/CTX@BLIP include increased survival time and decreased tumor volume. Following intravenous administration of Tf-ELE/CTX@BLIP, the tumor averaged fluorescence intensity was 65.2, 12.5, 22.1, 6.6, 2.6, 1.5 times weaker than that of the control, CTX solution, ELE solution, ELE/CTX@LIP, ELE/CTX@BLIP, Tf-ELE/CTX@LIP groups, respectively. Moreover, histopathological analyses demonstrated that Tf-ELE/CTX@BLIP were less toxic than the CTX solution. These results suggest that the active-targeting biomimetic liposomes, Tf-ELE/CTX@BLIP, is a promising nanoplatform for glioma chemotherapy.

Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System

“…The liposomes are promising transporters to deliver antitumoral drugs to GBM [27,[43][44][45][46][47]. However, there is evidence that lymphatic drainage of the brain is impaired in animals with GBM [57,58].…”

“…Liposomes are promising transporters to deliver anti-cancer drugs to GBM [27,[43][44][45][46][47]. They offer numerous advantages, such as the similarity of the liposomal bilayer with the cell membrane; liposomes provide low drug toxicity, stability, and increased circulation time as well as targeting liposomes by modifying with antibodies, and polypeptides [43,48,49].…”