The effect of targeted delivery of anti-TNF-α oligonucleotide into CD169+ macrophages on disease progression in lupus-prone MRL/lpr mice.
Systemic blockade of TNF-α via monoclonal antibodies and soluble receptors has shown considerable effects against several typical autoimmune disorders, but remains unconvincing for the treatment of lupus. Based on our previous study, a CD169(+) macrophage-specific therapy using TNF-α antisense oligonucleotides (ASO) was tested for its efficacy in MRL/lpr lupus-prone mice. ASO-containing cationic agarose hydrogel were injected into mice subcutaneously. Tissue distribution and cellular localization of ASO were determined. The therapeutic effects and possible mechanism were further studied in MRL/lpr lupus-prone mice. The results showed that specifically accumulation of the anti-TNF-α ASO in CD169(+) macrophages could significantly reduce TNF-α expression in CD169(+) macrophages and inhibit lymphocytes over-proliferation, finally resulted in the relief of the lupus-like symptoms of the animals. The nucleic acid drug based on CD169(+) macrophage-specific TNF-α regulation represents a potential therapeutic approach that may be valuable for lupus therapy.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
Zhen
Z
Huang
Zhengping
Z
Zhang
Yinhe
Y
Zha
Jialin
J
Liu
Yucui
Y
Jiang
Yang
Y
Yang
Juan
J
Shao
Xulun
X
Sun
Xin
X
Cai
Yuan
Y
Yin
Jiangning
J
Chen
Lei
L
Dong
Junfeng
J
Zhang
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D020007:Implants, Experimental; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D016376:Oligonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D012685:Sepharose; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D063267:Sialic Acid Binding Ig-like Lectin 1; D014409:Tumor Necrosis Factor-alpha; D012685:Sepharose