Probing the impact of sulfur/selenium/carbon linkages on prodrug nanoassemblies for cancer therapy

• DOI: 10.1038/s41467-019-11193-x
• Publication Date: 2019-07-19T10:03:00Z
• Authors: Bingjun Sun; Cong Luo; Xuanbo Zhang; Mengran Guo; Mengchi Sun; Han Yu; Qin Chen; Wenqian Yang; Menglin Wang; Shiyi Zuo; Pengyu Chen; Qiming Kan; Haotian Zhang; Yongjun Wang; Zhonggui He; Jin Sun
• Keywords: Rational design; Thioether

Tumor cells are characterized as redox-heterogeneous intracellular microenvironment due to the simultaneous overproduction of reactive oxygen species and glutathione. Rational design redox-responsive drug delivery systems is a promising prospect for efficient cancer therapy. Herein, six paclitaxel-citronellol conjugates synthesized using either thioether bond, disulfide selenoether diselenide carbon bond or carbon-carbon linkages. These prodrugs can self-assemble into uniform nanoparticles with ultrahigh drug-loading capacity. Interestingly, sulfur/selenium/carbon bonds significantly affect efficiency prodrug nanoassemblies. The angles/dihedral angles impact self-assembly, stability pharmacokinetics. redox-responsivity has remarkable influence on release cytotoxicity. Moreover, selenoether/diselenide possess unique ability produce species, which further improve cytotoxicity these prodrugs. Our findings give deep insight chemical linkages nanoassemblies provide strategies rational