Camptothecin (CPT) is a potent broad-spectrum antitumor agent with efficient therapeutic effect for various cancers. However, its application in glioma therapy has been impeded by the tumor immunosuppressive environment and blood–brain barrier (BBB)-associated drug delivery challenges. Herein, neurotransmitter analogs-modified liposomes (NTs-LIP) were prepared by doping lipidized tryptamine (Tryp) to co-deliver CPT and curcumin (CUR) for improved chemo-immunotherapy in glioma. The introduction of Tryp promotes the delivery efficiency of CPT and CUR across the BBB. CPT inhibits cell proliferation after cellular uptake of NTs-LIP, the combination of which with CUR downregulates the elevated expression of the programmed cell death 1 ligand 1 (PD-L1) caused by CPT to prevent the inactivation of T-cells and synergistically enhance chemo-immunotherapy efficacy. Furthermore, both Tryp and CUR interfere with the indoleamine 2,3-dioxygenase (IDO) pathway to reduce regulatory T cell (Treg)-mediated immunosuppression, exhibiting the potential to combine with PD-L1 inhibition for synergistic antitumor immunity. Taken together, this platform contributes towards targeted delivery and alleviation of the immunosuppressive environment in glioma therapy.
Neurodegenerative diseases bring heavy burden to our society. Methylmercury (MeHg) is a potent neurotoxin and causes neurodegenerative diseases like Minamata Disease. Therefore, finding ways to combat MeHg-induced neurodegeneration may shed light on the treatment of neurodegenerative diseases. This study investigated the efficacy of bismuth selenide nanoparticles (Bi 2 Se 3 NPs, nBS) in treating MeHg-induced neurodegeneration. MeHg-poisoned rats were orally given nBS (4 mg/kg) every other day for 21 days and then sacrificed. It was found that nBS improved neurobehavioral performance, alleviated hippocampus damage and intestinal barrier damage, reduced Hg accumulation, and promoted MeHg demethylation in MeHg-poisoned rats. In addition, nBS up-regulated the abundance of gut microbes such as Faecalibacterium, Bifidobacterium and Akkermansiaceae, and increased the levels of butyric acid in feces while reduced the concentration of isobutyric acid in the brains. At the same time, nBS reduced the secretion of inflammatory factors IL-6 and TNF-α in the brains, guts and serum, and regulated AHR/IDO expression in the guts and brains. In all, nBS treatment improved the health status of MeHg-poisoned rats through enhancing Hg excretion and MeHg demethylation, reshaping gut microbiota, and reducing neuroinflammation. These findings suggested that nBS supplementation is a promising approach to treat MeHg-induced neurodegeneration, which may shed lights on the treatment of neurodegenerative diseases.
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