Amelioration of colorectal cancer using negative lipidoid nanoparticles to encapsulate siRNA against APRIL by enema delivery mode.
A proliferation-inducing ligand (APRIL) is a key cell proliferation-regulatory molecule and have been investigated well enough in immunity regulation and a few of immune diseases. APRIL can stimulate tumor cell growth and is up-expressed in cancer tissues, especially in CRC (colorectal cancer). However, whether inhibition of APRIL can regulate tumor-relative genes expression in vivo and subsequently ameliorate the pathological progress of CRC remains obscure. To address this question, we developed a novel negative lipidoid nanoparticles (NLNs) encapsulating small interference RNA (siRNA) for selectively silencing APRIL in the parenchyma of CRC focus in vivo, which uptake proceeded through a lipid raft endocytotic pathway. Local enema delivery of APRIL-NLNs silenced APRIL in CRC cells and animal models, and then ameliorated experimentally the progress of CRC by suppressing CRC cell proliferation, metastasis, and apoptosis-related cytokine expression and did not affect the function of liver and kidneys and not trigger the immune response of CRC models. This study reveals APRIL to be a potential anti-CRC target by in vivo experiments, and suggests that the application of similar modes of siRNA delivery may be feasible in other therapeutic settings.
Medical Laboratory Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
Weifeng
W
Ding
Guihua
G
Wang
Keke
K
Shao
Feng
F
Wang
Hua
H
Huang
Shaoqing
S
Ju
Hui
H
Cong
Huimin
H
Wang
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D016503:Drug Delivery Systems; D004733:Enema; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000037:antagonists & inhibitors* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D008055:Lipids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13