Multifunctional targeting vinorelbine plus tetrandrine liposomes for treating brain glioma along with eliminating glioma stem cells

Abstract

Malignant brain glioma is the most lethal and aggressive type of cancer.Surgery and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood-brain barrier (BBB) restricts the movement of antitumor drugs from blood to brain,thus leading to the poor prognosis with high recurrence rate. In the present study,the targeting conjugates of cholesterol polyethylene glycol polyethylenimine(CHOL-PEG2000-PEI) and D-a-tocopheryl polyethylene glycol 1000 succinate vapreotide(TPGS1000-VAP) were newly synthesized for transporting drugs across the BBB andtargeting glioma cells and GSCs. The multifunctional targeting vinorelbine plustetrandrine liposomes were constructed by modifying the targeting conjugates. Thestudies were undertaken on BBB model, glioma cells, GSCs, and glioma-bearing mice.In vitro results showed that multifunctional targeting drugs-loaded liposomes withsuitable physicochemical property could enhance the transport drugs across the BBB,increase the intracellular uptake, inhibit glioma cells and GSCs, penetrate and destructthe GSCs spheroids, and induce apoptosis via activating related apoptotic proteins.In vivo results demonstrated that multifunctional targeting drugs-loaded liposomescould significantly accumulate into brain tumor location, show the specificity totumor sites, and result in a robust overall antitumor efficacy in glioma-bearing mice.These data suggested that the multifunctional targeting vinorelbine plus tetrandrineliposomes could offer a promising strategy for treating brain glioma.