Construction of a curcumin-siRNA co-delivery system based on mesoporous silica and its effect on M2-type polarization of macrophages

口腔疾病防治

卷:29

SONG Wen¹  LANG Kai²  LI Peihan³ 

[1] State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Air Force Medical University;

[2] 1.State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Air Force Medical University2. The Seventh Team of Second Brigades, College of Basic Medicine, The Air Force Medical University;

[3] 1.State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, The Air Force Medical University 2. The Seventh Team of Second Brigades, College of Basic Medicine, The Air Force Medical University;

关键词: macrophages;    m2 polarization;    arg-1;    curcumin;    rna interference;    sirna/mirna;    mesoporous silica nanoparticles;    co-delivery;   

DOI  :  10.12016/j.issn.2096⁃1456.2021.05.003

来源: DOAJ

【 摘 要 】

Objective To fabricate a co-delivery system of curcumin (CUR) and siRNA based on mesoporous silica nanoparticles (MSN) and investigate its potential application in inducing macrophage M2 polarization. Methods MSNs were synthesized using the conventional sol-gel method. The interior mesochannels were occupied by small-molecule CUR, while the exterior surface was adsorbed by cationic polymeric polyethyleneimine (PEI) to link the negatively charged siRNA molecules to formulate the (CUR@MSN)PEI/siRNA co-delivery system. The formulation process was monitored by transmission electron microscopy(TEM). The MTT assay was used to evaluate the cytotoxicity in RAW264.7 cells under various concentrations of nanoparticles. Confocal laser scanning microscopy and TEM were used to observe cell internalization using FAM-labeled siRNA. GAPDH-targeting siRNA was used to prepare nanoparticles and then was transfected into RAW264.7 cells to observe the silencing efficiency of target genes. The knockdown efficiency was examined by real-time quantitative PCR. The related control groups were untreated cells, CUR delivery only and the co-delivery of CUR and siRNA negative control. By loading miRNA-130a-3p antisense oligonucleotide (ASO) to transfect RAW264.7 cells, the effects on the polarization of macrophages were observed. The M2 polarization marker arginase 1 (Arg-1) was measured by western blotting. The related control groups were untreated cells, CUR delivery only and co-delivery of CUR and miRNA negative control. Results The (CUR@MSN)PEI/siRNA co-delivery system was successfully formulated. The nanoparticles exhibited dose-dependent cytotoxicity, and the cell viability was maintained over 90% when the nanoparticle concentration was less than 10 μg/mL. A high cell uptake efficiency was observed, and the target gene knockdown efficiency was greater than 80% (P < 0.05 vs. all the other groups). The CUR delivery-only group and co-delivery of the CUR-and miRNA-negative control group improved Arg-1 expression ~ 3-fold (P < 0.05 vs. untreated cells). Using the co-delivery of CUR and ASO, synergistic effects were obtained, and Arg-1 expression was increased ~ 8-fold (P < 0.05 vs. all the other groups). Conclusion The CUR-siRNA co-delivery system can effectively transfect macrophages and synergistically induce M2 polarization.

【 授权许可】

Unknown