A heparin-based nanogel system for redox and pH dual-responsive delivery of cisplatin

Abstract

Abstract Heparin recently has been discovered as a novel anti-cancer agent. The combinations of heparin with other agents was reported not only to reduce the undesired effects of free heparin and increase the cellular uptake of the delivered molecules, but also is the basis for the design and development of multi-stimulation response systems to improve their killing cancer cell efficiency at the target positions. This study aimed to design a redox and pH dual-responsive anticancer system based on heparin for cisplatin (CPT) therapy. Heparin was first cross-linked with Poloxamer 407 chains via disulfide bridges to form a redox-sensitive system Hep-P407. CPT was then encapsulated into the Hep-P407 system via the complex of Platin and carboxyl groups to form the redox/pH-responsive system CPT@Hep-P407. The obtained Hep-P407 systems were proved and characterized using specific techniques including 1H-NMR, zeta potential, Dynamic Light Scattering (DLS) and Fourier-transform infrared spectroscopy. The dual-responsive behavior to redox and pH of CPT@Hep-P407 was proved through DLS, zeta and in vitro release analysis meanwhile its cytotoxicity was investigated using Resazurin assay. The CPT@Hep-P407 system is expected to be a promising redox/pH-responsive anticancer system based on heparin for CPT therapy.