Redox-responsive amphiphilic camptothecin prodrug nanoparticles for targeted liver tumor therapy
Tumor cells targeting drug delivery system is of great importance to anti-tumor therapy in clinic. Owing to the overexpression of asialoglycoprotein receptor (ASGPR) on the hepatoma carcinoma cell membrane, conjugating of lactose on the surface of drug delivery system has already shown significant advantages of targeting tumor cells. In this work, a disulfide bond-conjugated prodrug targeting delivery system consisting of camptothecin (CPT) and lactose (LA) had been synthesized, and this conjugate was denoted as CPT-S-S-LA. Camptothecin and lactose were acted as chemotherapy drug and targeting ligand in the drug delivery system, respectively. Since CPT-S-S-LA was an amphiphilic compound, it could self-assemble into nanoparticles with diameter of around 100 nm. The CPT-S-S-LA nanoparticles displayed controllable drug release behavior in physiological environment. Unlike the free CPT, the CPT-S-S-LA nanoparticles could firstly assemble at the tumor sites via the enhanced permeability and retention (EPR) effect, and then be phagocytized by the tumor cells with ASGP receptor-mediated endocytosis. Finally, the antitumor agent CPT would be released for tumor cell killing in the high glutathione (GSH) concentration environment in tumor cells. The nanoparticles displayed favorable ability to target hepatoma carcinoma cell rather than the normal cell HUVEC in vitro. Both in vitro and in vivo studies demonstrated that CPT-S-S-LA nanoparticles displayed enhanced antitumor ability and reduced side effects. The active targeting prodrug delivering system should be a promising strategy for liver tumor therapy.