期刊
JOURNAL OF CONTROLLED RELEASE
卷 330, 期 -, 页码 641-657出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.12.036
关键词
Ginsenoside Rg3; Liposomes; Glioma targeting therapy; Paclitaxel; Tumor microenvironment remodeling; Blood brain barrier
资金
- National Natural Science Foundation of China [82074277, 8177391, 81690263]
- Development Project of Shanghai Peak Disciplines-Integrated Medicine [20180101]
The study found that using a liposomal system based on ginsenoside Rg3 can effectively improve the targeting of brain tumors, enhance the delivery of drugs, and play a beneficial role in anti-tumor treatment.
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 CLPs 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.
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