Abstract 2881: Injectable thermoresponsive hydrogel for the sustained delivery of triptolide in breast cancer treatment

Abstract

Abstract To avoid the narrow therapeutic window and take advantage of the anticancer efficacy of triptolide (TP), a major active component of Tripterygium wilfordii Hook.F., a novel thermo-responsive nano-micelle hydrogel was fabricated in present study for the sustained release of TP in breast tumor tissue. Briefly, the amphiphilic poloxamer 188-g-poly (N-isopropylacrylamide-co-acrylic acid) copolymer was synthesized by atomic transfer radical polymerization reaction and self-assembled into micelles in aqueous solution with CMC value of 2.6×10-3 mg/mL. TP encapsulated nanogel (TP/F68-g-(PNIPAAm-co-AAC)) exhibited the sol-gel phase transition at 32°C with a narrow size distribution (about 50.16 nm) and sustained drug release in vitro. And then, the TP-loaded nanogel significantly inhibited the cell proliferation against human breast cancer MDA-MB-231 and MCF-7 cells, as well as the induction of cell apoptosis and cell cycle arrest activity. Moreover, we also found the superior anti-angiogenic activities of TP nanogel in both HUVEC and rat aortic ring model when compared to free TP. As expected, mediated by the 4T1 mouse breast cancer model, we demonstrated that a single injection of the TP-loaded nanogel system resulted in the long detention time in tumor tissue due to its thermo-responsive capacity. Moreover, the novel nanogel remarkably enhanced anticancer efficacy and reduced the side effects, when compared with the multiple injections of free TP. Therefore, the injectable thermo-responsive nanogel provided a potential strategy for the efficient delivery of TP with a sustained release manner in breast cancer treatment. Citation Format: Jingjing Li, Jinming Zhang, George Pak-Heng Leung. Injectable thermoresponsive hydrogel for the sustained delivery of triptolide in breast cancer treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2881.