Precision\nDelivery of Binary Cooperative Nanodrugs\nSelf-Assembled by Berberine Glycyrrhetinic Acid Salts for Hepatocellular\nCarcinoma Treatment

Berberine\n(BB) has demonstrated significant inhibitory effects\non tumorigenesis and progression. However, its clinical application\nis hindered by challenges such as low bioavailability due to limited\ncell membrane permeability, nontargeted accumulation away from solid\ntumors, and increased toxicity associated with intravenous administration.\nTo overcome these challenges, a lipophilic salt-forming strategy was\nemployed to enhance lipophilicity, thereby promoting membrane permeability\nand targetability for tumor accumulation while simultaneously mitigating\nthe toxicity associated with intravenous injection. <i>In vitro</i> findings revealed an almost 10-fold increase in fluorescence intensity\nwith BB-GA NDs compared to BB alone. Furthermore, selective cytotoxicity\nagainst tumor cells exhibited a 4-fold elevation compared to normal\ncells. <i>In vivo</i> results underscored the remarkable\ntumor-selective accumulation of BB-GA NDs, effectively mitigating\nthe intravenous injection toxicity associated with pure BB. The self-assembly\nof binary cooperative nanodrugs utilizing berberine glycyrrhetinic\nacid salts opens up innovative possibilities for drug delivery systems\nin traditional Chinese medicine.