Probing the Impact of Sulfur/selenium/carbon Linkages on Prodrug Nanoassemblies for Cancer Therapy

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Jul 21

PMID 31324811

Citations 70

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

Affiliations

Soon will be listed here.

Abstract

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

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