The β-glucan nanotube carrier achieves detoxification and efficacy enhancement of celastrol in intrahepatic cholangiocarcinoma therapy by increasing targeted controlled release and macrophage polarization

Celastrol (Cel) is a monomer from a famous traditional Chinese medicine named Tripterygium wilfordii Hook. f. Cel has shown great potential in treating intrahepatic cholangiocarcinoma (ICC) but still faces problems, including poor water solubility, high toxicity, and lack of targeting ability. Thus, the present work constructed a drug-delivery system using black fungus polysaccharide self-assembled -nanotubes (BFP). Cel-loaded nanotubes (BFP-Cel) were confirmed to have a high loading content of Cel (38 %), liver targeting, and enzyme-controlled release abilities. Moreover, BFP carriers could significantly increase the uptake efficiency of Cel by tumor cells. In vivo experiments showed that BFP-Cel could effectively inhibit tumor growth and reduce the physiological toxicity of Cel. Furthermore, BFP, as a carrier, could regulate the immune microenvironment in the liver through the activation of macrophages and play an immunomodulatory role. In summary, the BFP nanotube carrier could achieve detoxification and efficacy enhancement of Cel in treating ICC by increasing the targetability, controlled release ability, cell-uptake effect, and regulation of the immune microenvironment.