Vascular endothelial growth factor (VEGF) plays important roles in the angiogenesis process and is correlated with high proliferation and metastasis of breast cancer, particularly in triple negative breast cancer (TNBC). Downregulation of VEGF expression with siRNA in cancer cells is therefore a potential strategy for TNBC treatment. A polyethylene glycol based bio-degradable, linear multiblock polymer was synthesized and conjugated with branched low-molecular-weight poly(ethyleneimine) (PEI) to form nanocomplexes with a VEGF siRNA. The nanocomplex can protect siRNA from serum degradation and deliver the VEGF siRNA into TNBC cells with 72% silencing activity and low cytotoxicity. In vitro activity studies showed that the siRNA nanocomplexes significantly inhibit 64% migration and 67% invasion of TNBC cells. Moreover, the nanocomplex exhibited efficient tumor penetration in a 3D tumor spheroid model, suggesting a good penetration capability of the nanocomplex in tumor microenvironment in vivo. More importantly, the VEGF siRNA nanocomplex efficiently inhibit tumor growth in vivo and successfully downregulate VEGF expression in the tumor. These results suggested that VEGF siRNA is a promising anti-tumor agent for TNBC therapy, and the PEI 1800 conjugated bio-degradable multiblock polymer is a promising system to deliver siRNAs to TNBC cells.

Note: This abstract was not presented at the meeting.

Citation Format: Yuanke Li, Zhen Zhao, Kun Cheng. Development of a polyethylenimine conjugated liner multiblock polymer to deliver VEGF siRNA for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3637.