@article{ee4be3f0d5434b9aa79528f563a08df0,
title = "Promoting the Delivery of Nanoparticles to Atherosclerotic Plaques by DNA Coating",
abstract = " 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.",
keywords = "atherosclerosis, cardiovascular diseases, macrophages, nanoparticles, oligonucleotides, targeted delivery",
author = "Lei Zhang and Tian, {Xiao Yu} and Chan, {Cecilia K. W.} and Qianqian Bai and Cheng, {Chak Kwong} and Chen, {Francis M.} and Cheung, {Maggie S. H.} and Bohan Yin and Hongrong Yang and Yung, {Wing Yin} and Zhong Chen and Fei Ding and Leung, {Ken Cham Fai} and Chuan Zhang and Yu Huang and Lau, {James Y. W.} and Choi, {Chung Hang Jonathan}",
note = "Funding Information: This work was supported by a General Research Fund (project no. 14302916) from the Research Grants Council (RGC) of Hong Kong, the National Science Foundation of China (NSFC)/RGC Joint Research Scheme (project no. N_CUHK434/16), Shun Hing Institute of Advanced Engineering (project no. BME-8115047), and the Chow Yuk Ho Technology Centre for Innovative Medicine (project no. TIMSG 15/16-4) at The Chinese University of Hong Kong (CUHK). C.H.J.C. acknowledges a Startup Allowance and a Croucher Innovation Award from the Croucher Foundation. X.Y.T. acknowledges a Health and Medical Research Fund (HMRF-RFS-01150057). C.Z. acknowledges support from the NSFC (project nos. 21504053 and 21661162001). Y.H. acknowledges a Collaborative Research Fund from the RGC (project no. C4024-16W). We thank Freddie Kwok (School of Life Sciences, CUHK) for assistance with cryo-sectioning, Chun Wah Lin (Department of Chemistry, CUHK) for assistance with ICP-OES, and Josie Lai (School of Biomedical Sciences, CUHK) for assistance with biological TEM imaging. Funding Information: This work was supported by a General Research Fund (project no. 14302916) from the Research Grants Council (RGC) of Hong Kong, the National Science Foundation of China (NSFC)/RGC Joint Research Scheme (project no. N_CUHK434/16), Shun Hing Institute of Advanced Engineering (project no. BME-8115047), and the Chow Yuk Ho Technology Centre for Innovative Medicine (project no. TIMSG 15/16-4) at The Chinese University of Hong Kong (CUHK). C.H.J.C. acknowledges a Startup Allowance and a Croucher Innovation Award from the Croucher Foundation. X.Y.T. acknowledges a Health and Medical Research Fund (HMRF-RFS-01150057). C.Z. acknowledges support from the NSFC (project nos. 21504053 and 21661162001). Y.H. acknowledges a Collaborative Research Fund from the RGC (project no. C4024-16W). We thank Freddie Kwok (School of Life Sciences, CUHK) for assistance with cryo-sectioning, Chun Wah Lin (Department of Chemistry, CUHK) for assistance with ICP-OES, and Josie Lai (School of Biomedical Sciences, CUHK) for assistance with biological TEM imaging. Publisher copyright: {\textcopyright} 2018 American Chemical Society",
year = "2019",
month = apr,
day = "17",
doi = "10.1021/acsami.8b17928",
language = "English",
volume = "11",
pages = "13888--13904",
journal = "ACS Applied Materials and Interfaces",
issn = "1944-8244",
publisher = "American Chemical Society",
number = "15",
}
