title: Targeted delivery of oligonucleotides into tumor-associated macrophages for cancer immunotherapy.
abstract: Tumor-associated macrophages (TAMs) have been proven to be a driving force in the initiation, proliferation, metastasis and angiogenesis of various tumors. Specifically, alterations in the functions of TAMs exhibited inhibitory effects on tumor growth. However, there is currently no research being conducted on the targeting delivery of drugs into TAMs for cell-specific tumor immunotherapy. In the present study, we developed a TAMs targeted delivery system that is triggered by the acidic microenvironment in the tumor to release a TAMs-recognizing nano-complex loaded with oligonucleotides. By using this system, we demonstrated a significant anti-tumor effect of an oligonucleotide combination of CpG oligonucleotide, anti-IL-10 and anti-IL-10 receptor oligonucleotides. These nucleic acid drugs delivered by the delivery system accumulated in the TAMs of an allograft hepatoma murine model by intravenous injection, suppressed the pro-tumor functions and stimulated the anti-tumor activities of TAMs. More importantly, the nucleic acid drug-based immune-regulation was restricted to the tumor microenvironment and did not cause an upregulation of serum inflammatory cytokines. Our present study provides an effective therapeutic strategy for regulating cell-specific functions using nucleic acid drugs.
authors: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors: Zhen
authors: Z
authors: Huang
authors: Zhengping
authors: Z
authors: Zhang
authors: Yucui
authors: Y
authors: Jiang
authors: Dachuan
authors: D
authors: Zhang
authors: Jiangning
authors: J
authors: Chen
authors: Lei
authors: L
authors: Dong
authors: Junfeng
authors: J
authors: Zhang
mesh_terms: D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry; D006639:Histidine / Q000008:administration & dosage / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008113:Liver Neoplasms / Q000628:therapy*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D053701:Receptors, Interleukin-10 / Q000235:genetics / Q000276:immunology; D014162:Transfection / Q000379:methods*
chemical_list: D000464:Alginates; D003911:Dextrans; D009841:Oligonucleotides; D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D011092:Polyethylene Glycols; D006639:Histidine