Issue 108, 2014

pH and reduction dual responsive cross-linked polyurethane micelles as an intracellular drug delivery system

Abstract

Nano-vehicles that exhibit enhanced stability in blood circulation while spontaneously releasing therapeutic cargos at pathological sites in response to specific biological triggers are of interest for on-demand drug delivery. In this work, disulfide cross-linked polyurethane micelles (CL-PUMs) that respond to pH change and an intracellular reducing agent were developed. The micelles were prepared by cross-linking of poly(ethylene glycol)–polyurethane multiblock copolymers containing tertiary amino and cyclic disulfide moieties via a thiol–disulfide exchange reaction. The CL-PUMs tended to swell or decompose under a weakly acidic environment or in the presence of an intracellular reducing agent, glutathione (GSH), likely owing to the protonation of the tertiary amino groups and cleavage of the disulfide cross-linking bonds. The doxorubicin (DOX)-loaded CL-PUMs suppressed the initial burst release at pH 7.4 without GSH, while they displayed a triggered drug release manner in response to an acidic environment and GSH. It was found that the intracellular DOX release of the DOX-loaded CL-PUMs in HepG2 cells was accelerated by an acidic environment or enhanced intracellular GSH concentration. Moreover, the time-dependent cytotoxicity against HepG2 and HeLa cells of the DOX-loaded CL-PUMs was confirmed by an MTT assay. Overall, due to the enhanced stability, selective swelling and decomposition properties in response to intracellular micro-environments, the pH- and reduction-sensitive polyurethane cross-linked nano-carriers can serve as a potential system for intracellular drug delivery.

Graphical abstract: pH and reduction dual responsive cross-linked polyurethane micelles as an intracellular drug delivery system

Supplementary files

Article information

Article type
Paper
Submitted
10 Nov 2014
Accepted
14 Nov 2014
First published
14 Nov 2014

RSC Adv., 2014,4, 63070-63078

Author version available

pH and reduction dual responsive cross-linked polyurethane micelles as an intracellular drug delivery system

S. Yu, C. He, Q. Lv, H. Sun and X. Chen, RSC Adv., 2014, 4, 63070 DOI: 10.1039/C4RA14221G

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