Enhanced cytotoxic T lymphocytes recruitment targeting tumor vasculatures by endoglin aptamer and IP-10 plasmid presenting liposome-based nanocarriers

作者：Xiaomei Yang, Jing Zhao, Siliang Duan, Xiaoqiong Hou, Xi Li, Zixi Hu, Zhuoran Tang, Fengzhen Mo, Xiaoling Lü · 发表于：Theranostics · 年份：2019 · DOI：10.7150/thno.33383 · 被引用次数：32 · 研究领域：Nanoplatforms for cancer theranostics、Immunotherapy and Immune Responses、Immune cells in cancer

Background: Adequate recruitment of highly active tumor antigen-specific cytotoxic T lymphocytes (CTLs) remains a major challenge in cancer immunotherapy. Objective: To construct liposome (LP)-based nanocapsules with surface endoglin aptamer (ENG-Apt) encapsulating mouse interferon-inducible protein-10 (mIP-10), with the ability to target mouse tumor vascular endothelial cells (mTECs) and enhance CTLs targeting and recruitment to the tumor vasculature. Methods: ENG-Apt/mIP-10-LP nanocapsules were prepared by grafting DSPE-PEG2000-ENG-Apt on the surface of liposomes containing mIP-10 plasmids, characterized and assessed for the cell binding specificity in vitro. The tumor-targeting ability of ENG-Apt/mIP-10-LP nanocapsules was evaluated in vivo. The anti-tumor efficacy of ENG-Apt/mIP-10-LP nanocapsules treatment, as well as the combination treatment of ENG-Apt/mIP-10-LP nanocapsules and adoptive TRP2CD8 + T cells, were both tested in melanoma-bearing mice, by evaluation of the tumor volume and the mouse survival time. To discuss the anti-tumoral mechanism of ENG-Apt/mIP-10-LP nanocapsules-based therapies, IFN- secretion, proportion of TRP2CD8 + T cells among TILs, MDSCs in the tumor microenvironment and Tregs in the spleen, were determined after the treatments. Proliferation and apoptosis of tumor cells, and tumor angiogenesis were also assessed.