Multifunctional ginsenoside Rg3-based liposomes for glioma targeting therapy.

Liposomes have been widely used for targeted drug delivery. However, nonselective distribution, low blood-brain barrier penetration, and the disadvantages of cholesterol greatly limit the application of conventional liposomes in the treatment of brain tumors. In the present study, we aimed to develop a multifunctional ginsenoside Rg3-based liposomal system (Rg3-LPs). Compared to cholesterol liposomes (C-LPs), Rg3-LPs not only significantly improved cellular uptake and penetration across glioma spheroids in vitro, but also remarkably enhanced active glioma targeting and intratumoral diffusion capability in vivo. Paclitaxel-loaded Rg3-LPs (Rg3-PTX-LPs) exhibited a substantially stronger anti-proliferation effect on C6 glioma cells than paclitaxel-loaded C-LPs and re-educated tumor-associated macrophages from the protumor M2 phenotype to the antitumor M1 phenotype in vivo. Rg3-PTX-LPs significantly prolonged median survival time of intracranial C6-bearing mice/rats by activating the immune microenvironment in glioma, facilitating T-cell immune responses with expansion of the CD8 T-cell population, increasing the M1/M2 ratio, and decreasing regulatory T and myeloid-derived suppressor cells. Together, the results demonstrated that ginsenoside Rg3 is a good alternative for cholesterol in drug delivery liposomes and has a synergistic effect with loaded anticancer drugs. Rg3-PTX-LPs can serve as a multifunctional potential drug for the treatment of glioma.