IL-4Rα aptamer-liposome-CpG oligodeoxynucleotides suppress tumour growth by targeting the tumour microenvironment.
Tumour immunosuppressive microenvironments inhibit antigen-specific cellular responses and interfere with CpG-mediated immunotherapy. Overcoming tumour microenvironment (TME) immunosuppression is an important strategy for effective therapy. This study investigated the ability of a tumour-targeting IL-4Rα aptamer-liposome-CpG ODN delivery system to introduce CpG into tumours and overcome the immunosuppressive TME. The IL-4Rα-liposome-CpG delivery system was prepared. FAM-CpG visualisation was used to demonstrate tumour targeting in vitro and in vivo. Anti-tumour effects of this delivery system were evaluated in CT26 tumour-bearing mice. Mechanisms for conquering the TME were investigated. FAM-CpG was better distributed into the tumours upon treatment with IL-4Rα-liposome-FAM-CpG compared to distribution in the control group in vitro and in vivo. IL-4Rα-aptamer-liposome-CpG treatment inhibited distinct myeloid-derived suppressor cell populations in tumours and bone marrow. Similar profiles were observed for regulatory T cells in tumours. In CT26 tumour-bearing mice, IL-4Rα-liposome-CpG treatment exhibited enhanced anti-tumour activity. Increased mRNA levels of TNF-α, IL-2, and IL-12, and decreased mRNA levels of VEGF, IL-6, IL-10, MMP9, arginase-1, inducible NOS, CXCL9, p-Stat3, and NF-κB were observed in tumours upon IL-4R-liposome-CpG-treatment. The results suggested that pharmacologic targeting by the IL-4R aptamer-liposome-CpG system improves TME therapeutic benefit and provides a rationale for cancer immunotherapies.
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.|b Department of Pharmacology, Guangxi Medical University , Nanning, People's Republic of China.
Yu-Jie
YJ
Liu
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.|b Department of Pharmacology, Guangxi Medical University , Nanning, People's Republic of China.
Xiao-Qian
XQ
Dou
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.
Fang
F
Wang
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.
Jing
J
Zhang
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.
Xiao-Lin
XL
Wang
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.
Gui-Li
GL
Xu
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.
Shen-Si
SS
Xiang
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.
Xin
X
Gao
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.
Jie
J
Fu
a Department of Pharmacology and Toxicology , Beijing Institute of Radiation Medicine , Beijing , People's Republic of China.|b Department of Pharmacology, Guangxi Medical University , Nanning, People's Republic of China.
Hai-Feng
HF
Song
D000818:Animals; D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009374:Neoplasms, Experimental / Q000473:pathology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D059016:Tumor Microenvironment / Q000187:drug effects*
D052157:Aptamers, Nucleotide; C408982:CPG-oligonucleotide; D053662:Interleukin-4 Receptor alpha Subunit; D009838:Oligodeoxyribonucleotides
CpG; IL-4Rα; aptamer; myeloid-derived suppressor cell; tumour microenvironment