Inhibition of tumor growth and normalization of immune responses in the tumor microenvironment (TME) are critical issues for improving cancer therapy. However, in the treatment of glioma, effective nanomedicine has limited access to the brain because of the blood-brain barrier (BBB). Fudan University researchers have demonstrated nano-sized ginseng-derived exosome-like nanoparticles (GENs) consisting of phospholipids including various bioactive components, and evaluated anti-tumor immune responses in T cells and Tregs to inhibit tumor progression. It was found that the enhanced targeting ability of GENs to the BBB and glioma induced a significant therapeutic effect and exhibited strong efficacy in recruiting M1 macrophage expression in the TME. GENs were demonstrated to be successful candidates in glioma therapeutics both in vitro and in vivo, suggesting excellent potential for inhibiting glioma progression and regulating tumor-associated macrophages (TAMs).
Isolation and characterization of ginseng-derived exosome-like nanoparticles (GENs)
a A schematic illustration of the isolation process of GENs from fresh ginseng. Ginseng juice was sequentially centrifuged at low and high velocity of speed to isolate GENs. The sucrose cushion method was employed by layering sucrose at concentrations of 68% and 27%. GENs were purified by a buoyant density from 1.13 to 1.19 g/mL using a density gradient method. After the purification of GENs, the cellular toxicity and therapeutic efficiency of GENs were evaluated by in vitro and in vivo analyses. b The sucrose cushion method to prevent disruption of the extracellular vesicles (EVs) and contaminants caused by excessive aggregates of EVs during centrifugation (right). c The specific layer between 8 and 30% of sucrose was achieved and the concentration of 2.24 × 10.13 particles/mL and size distribution were determined with a serial dilution of GENs by nanoparticle tracking analysis (NTA). The round-shaped morphology of GENs was observed by transmission electron microscopy (TEM; inset). d The size and zeta potential of GENs were measured at 37 ℃ by dynamic light scattering (DLS). e A graph of lipidomic analysis was reported as the percentage of the components of lipids of GENs. f The concentration of ginsenosides of GENs was determined by high performance liquid chromatography (HPLC). wax esters (WE), triglycerides (TG), sulfoquinovosyldiacylglycerol (SQDG), sphingosine (So), phosphatidylserine (PS), phosphatidylinositol phosphate (PIP), phosphatidylinositol (PI), phosphatidylgylcerols (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidic acid (PA), monogalactosylmonoacylglycerol (MGMG), monogalactosylacylglycerols (MGDG), monoacylglycerol (MG), lysophosphatidylglycerol (LPG), lysophosphatidylethanolamine (LPE), lysophophatidylcholine (LPC), lysophosphatidic acid (LPA), digalactosylmonoacylglycerol (dgmg), digalactosyldiacylglycerol (DGDG), diacylglycerol (DG), coenzyme (Co), cardiolipin (CL), ceramide 1-phosphates (CerP), CerG3GNAc1, diglycosylceramide (CerG2), glucosylceramide (CerG1), ceramides (Cer), acylglucosyl-sitosterol esters (AGlcSiE)