Promoting the Delivery of Nanoparticles to Atherosclerotic Plaques by DNA Coating

Lei Zhang, Xiao Yu Tian, Cecilia K.W. Chan, Qianqian Bai, Chak Kwong Cheng, Francis M. Chen, Maggie S.H. Cheung, Bohan Yin, Hongrong Yang, Wing Yin Yung, Zhong Chen, Fei Ding, Ken C F LEUNG, Chuan Zhang, Yu Huang, James Y.W. Lau, Chung Hang Jonathan Choi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13888-13904
Number of pages17
JournalACS applied materials & interfaces
Volume11
Issue number15
DOIs
Publication statusPublished - 17 Apr 2019

Scopus Subject Areas

  • Materials Science(all)

User-Defined Keywords

  • atherosclerosis
  • cardiovascular diseases
  • macrophages
  • nanoparticles
  • oligonucleotides
  • targeted delivery

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