Novel facile thermosensitive hydrogel as sustained and controllable gene release vehicle for breast cancer treatment

Abstract

The current research process in gene therapy for cancer treatment has brought much attention due to its great potential for both inherited and acquired diseases. Precise accumulation in target site and on-demand release of drug is critical factors for the efficient gene therapy. Since the delivery of suitable gene largely depends on the delivery carrier, the design of suitable gene delivery vehicle for the sustained gene release in target site are attracting increasingly interest among the researchers. In this report, an effective and relatively convenient gene delivery platform is developed by the electrostatic interaction between negative charged survivin antisense oligonucleotide (Sur-ASON) and positive charged PHB-b-PDMAEMA (PHB-P) co-polymer and then the induction of thermosensitive PF127 hydrogel. The prepared hydrogel could achieve a sustained gene release property in the tumor region after injection, thus to enhance the effect of Survivin antisense oligonucleotide and inhibit P-gp impaired drug uptake simultaneously. In vivo anti-tumor efficacy and H&E staining indicated that Sur-ASON/PHB-P/PF127 hydrogel was greatly effective in enhancing the treatment effects of Sur-ASON while reducing the degradation and the possible adverse side effects, and this novel hydrogel could achieve the controlled gene release up to maximum 16 days. The aforementioned properties indicated that the novel hydrogel could be applied as a promising and convenient anti-cancer agent for anticancer therapy with minimum injection frequency to possibly increase patient compliance.

Keywords: Gene therapy; Multidrug resistance; PF127 hydrogel; Sustained release.