EGFP-EGF1-conjugated poly (lactic-co-glycolic acid) nanoparticles as a carrier for the delivery of CCR2- shRNA to atherosclerotic macrophage in vitro

Reducing macrophage recruitment by silencing chemokine (C-C motif) receptor 2 (CCR2) expression is a promising therapeutic approach against atherosclerosis. However the transfection of macrophages with siRNA is often technically challenging. EGFP-EGF1-conjugated poly (lactic-co-glycolic acid) (PLGA)...

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Bibliographic Details
Published in:	Scientific reports 2020-11, Vol.10 (1), p.19636, Article 19636
Main Authors:	Wu, Zhilin, Chen, Chen, Luo, Jiajia, Davis, Jacques R J, Zhang, Bo, Tang, Liang, Shi, Wei, Liao, Danying
Format:	Article
Language:	eng
Subjects:	Animals Arteriosclerosis Atherosclerosis Atherosclerosis - drug therapy Atherosclerosis - metabolism Biocompatible Materials - chemistry CC chemokine receptors CCR2 protein Cell Line Coumarin Cytotoxicity Drug Carriers - administration & dosage Drug delivery Drug Delivery Systems Feasibility studies Flow cytometry Fluorescence microscopy Glycolic acid Green Fluorescent Proteins - chemistry Inflammation Macrophages Macrophages - drug effects Macrophages - metabolism Mice Monocyte chemoattractant protein 1 Monocytes mRNA Nanoparticles Nanoparticles - administration & dosage Nanoparticles - chemistry Peptide Elongation Factor G - chemistry Polylactic Acid-Polyglycolic Acid Copolymer - chemistry Polylactide-co-glycolide Receptors, CCR2 - antagonists & inhibitors Receptors, CCR2 - genetics Recombinant Fusion Proteins - chemistry RNA, Small Interfering - administration & dosage RNA, Small Interfering - chemistry RNA, Small Interfering - pharmacology siRNA Tissue factor Transfection
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Summary:	Reducing macrophage recruitment by silencing chemokine (C-C motif) receptor 2 (CCR2) expression is a promising therapeutic approach against atherosclerosis. However the transfection of macrophages with siRNA is often technically challenging. EGFP-EGF1-conjugated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (ENPs) have a specific affinity to tissue factor (TF). In this study, the feasibility of ENPs as a carrier for target delivery of CCR2-shRNA to atherosclerotic cellular models of macrophages was investigated. Coumarin-6 loaded ENPs were synthesized using a double-emulsion method. Fluorescence microscopy and flow cytometry assay were taken to examine the uptake of Coumarin-6 loaded ENPs in the cellular model. Then a sequence of shRNA specific to CCR2 mRNA was constructed and encapsulated into ENPs. Target delivery of CCR2-shRNA to atherosclerotic cellular models of macrophages in vitro were evaluated. Results showed more uptake of ENPs by the cellular model than common PLGA nanoparticles. CCR2-shRNA loaded ENPs effectively silenced CCR2 gene in the atherosclerotic macrophages and exhibited a favorable cytotoxic profile to cultured cells. With their low cytotoxicity and efficient drug delivery, ENP could be a useful carrier for target delivery of CCR2-shRNA to inflammatory monocytes/macrophages for the therapy against atherosclerosis.
ISSN:	2045-2322 2045-2322