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

: Adequate recruitment of highly active tumor antigen-specific cytotoxic T lymphocytes (CTLs) remains a major challenge in cancer immunotherapy. : 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. : ENG-Apt/mIP-10-LP nanocapsules were prepared by grafting DSPE-PEG-ENG-Apt on the surface of liposomes containing mIP-10 plasmids， characterized and assessed for the cell binding specificity . The tumor-targeting ability of ENG-Apt/mIP-10-LP nanocapsules was evaluated . 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-γ 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. : The prepared ENG-Apt/mIP-10-LP nanocapsules possess an adequate nanometric size， good stability， high specificity to mTECs and tumor sites， along with the ability to induce mIP-10 expression and . Treatment of ENG-Apt/mIP-10-LP nanocapsules demonstrated CTLs enrichment into the tumor site， which inhibited tumor cell proliferation and angiogenesis， as well as promoted tumor-cell apoptosis， leading to a decrease in tumor progression and prolonged survival time in melanoma tumor-bearing mice. In addition， the proportion of MDSCs and Tregs was found to decrease. The combination of ENG-Apt/mIP-10-LP nanocapsules with adoptive TRP2CD8 T cells， showed stronger abilities in inhibiting tumor growth and increasing animal survival time， thereby displayed an enhanced anti-melanoma tumor efficacy， due to the recruitment of both endogenous CD8 T cells and exogenous TRP2CD8 T cells . : ENG-Apt/mIP-10-LP nanocapsules could enhance the recruitment of both endogenous and exogenous CTLs specifically targeting melanoma tumor vasculatures and exert anti-tumoral effect， therefore provides a potentially novel strategy for tumor immunotherapy.