Promoting the delivery of nanoparticles to atherosclerotic plaques by DNA coating
Publication in refereed journal


摘要Many nanoparticle-based carriers to atherosclerotic plaques contain peptides, lipoproteins, and sugars, yet the application of DNA-based nanostructures for targeting plaques remains infrequent. In this work, we demonstrate that DNA-coated superparamagnetic iron oxide nanoparticles (DNA-SPIONs), prepared by attaching DNA oligonucleotides to poly(ethylene glycol)-coated SPIONs (PEG-SPIONs), effectively accumulate in the macrophages of atherosclerotic plaques following an intravenous injection into apolipoprotein E knockout (ApoE–/–) mice. DNA-SPIONs enter RAW 264.7 macrophages faster and more abundantly than PEG-SPIONs. DNA-SPIONs mostly enter RAW 264.7 cells by engaging Class A scavenger receptors (SR-A) and lipid rafts and traffic inside the cell along the endolysosomal pathway. ABS-SPIONs, nanoparticles with a similarly polyanionic surface charge as DNA-SPIONs but bearing abasic oligonucleotides also effectively bind to SR-A and enter RAW 264.7 cells. Near-infrared fluorescence imaging reveals evident localization of DNA-SPIONs in the heart and aorta 30 min post-injection. Aortic iron content for DNA-SPIONs climbs to the peak (∼60% ID/g) 2 h post-injection (accompanied by profuse accumulation in the aortic root), but it takes 8 h for PEG-SPIONs to reach the peak aortic amount (∼44% ID/g). ABS-SPIONs do not appreciably accumulate in the aorta or aortic root, suggesting that the DNA coating (not the surface charge) dictates in vivo plaque accumulation. Flow cytometry analysis reveals more pronounced uptake of DNA-SPIONs by hepatic endothelial cells, splenic macrophages and dendritic cells, and aortic M2 macrophages (the cell type with the highest uptake in the aorta) than PEG-SPIONs. In summary, coating nanoparticles with DNA is an effective strategy of promoting their systemic delivery to atherosclerotic plaques.
著者Zhang Lei, Tian Xiao Yu, Chan Cecilia Ka Wing, Bai Qianqian, Cheng Chak Kwong, Chen Francis M, Cheung Maggie SH, Yin Bohan, Yang Hongrong, Yung Wing Yin, Chen Zhong, Ding Fei, Leung Ken Cham-Fai, Zhang Chuan, Huang Yu, Lau James Yun Wong, Choi Chung Hang Jonathan
期刊名稱ACS Applied Materials and Interfaces
出版社American Chemical Society
頁次13888 - 13904
關鍵詞atherosclerosis, cardiovascular diseases, macrophages, nanoparticles, oligonucleotides, targeted delivery

上次更新時間 2020-15-10 於 03:00