Enhanced delivery of artesunate by stimuli-responsive polymeric micelles for lung tumor therapy

Abstract Artesunate (ART) as a traditional chinese medicine has been reported to have a good antitumor effect on some cancers. However, the poor hydrophilicity and instability in the intestine limit its bioavailability and further application. Herein, this work reported a redox-sensitive micelle system encapsulating ART to enhance the therapeutic effect on lung tumor. Specifically, K5 capsular polysaccharide-SS- d -α-tocopheryl succinate (K5-SS-TOS, KSST) copolymers can self-assemble to form micelles and effectively load ART into the hydrophobic core. Simultaneously, redox-insensitive K5 capsular polysaccharide- d -α-tocopheryl succinate (K5-TOS, KT) copolymers were synthesized as control. ART-loaded micelles (ART/KSST) with a spherical particle size had good polydispersity. The drug loading content and entrapment efficiency of the ART/KSST were (13.5 ± 0.92) % and (81.09 ± 2.61) %, respectively. Moreover, ART/KSST can release ART quickly in the presence of glutathione, showing a good redox release behavior. In addition, the ART loaded micelles had negligible toxicity to normal cells. However, ART/KSST which can be uptaken through energy-dependent pathways by A549 cells showed higher cytotoxicity than ART/KT. The results suggested that disulfide bond can be ruptured in the tumor cells, resulting in disintegration of the micelle structure and fast release of ART to achieve better therapeutic effect. Therefore, the redox-sensitive KSST copolymers as potential nanocarriers can deliver ART effectively to improve the therapeutic effect of lung tumors.