Redox-responsive nanoparticles based on Chondroitin Sulfate and Docetaxel prodrug for tumor targeted delivery of Docetaxel

Abstract

In this paper, a novel redox-responsive nanoparticles has been designed for targeted delivery of docetaxel (DTX). Chondroitin sulfate (CS) was used to construct the nanoparticles due to the ability of tumor targeting through binding with CD44 receptor that overexpresses on the surfaces of various tumor cells. A redox-responsive small-molecular DTX prodrug was prepared through modifying with cystamine containing disulfide bonds (Cys-DTX). Then the DTX prodrug was grafted to the CS to construct the amphiphilic polymer (CS-ss-DTX). Further, Cys-DTX/CS-ss-DTX nanoparticles were formed by self-assembly of amphiphilic polymer and incorporation of free Cys-DTX prodrug. This category of nanosized DTX delivery system was expected for not only exhibiting high permeability and cytotoxicity of Cys-DTX prodrug, but also targeting transportation of encapsulated redox-responsive Cys-DTX prodrug. According to results of related researches on physicochemical properties and biological evaluation, the novel redox-responsive Cys-DTX/CS-ss-DTX nanoparticles increased amount of DTX released from the nanoparticles in reductive environment, improved permeability in tumor tissues, enhanced cytotoxicity and decreased side effects compared with free DTX. All of these results showed that this kind of Cys-DTX/CS-ss-DTX nanoparticles were worthy of being expectation in tumor chemotherapy in future.

Keywords: Chondroitin Sulfate: CAS: 9007-28-7; Chondroitin sulfate; Compound CID: 148124; Compound CID: 24766; Compound CID: 5941; Cystamine： CAS: 56-17-7; Docetaxel：CAS: 114977-28-5; Polymeric nanoparticles; Redox responsive; Small molecular DTX prodrug; Tumor targeted delivery.