Tailoring Nanostructure Morphology for Enhanced Targeting of Dendritic Cells in Atherosclerosis

Sijia Yi, Sean David Allen, Yu Gang Liu, Brian Zhou Ouyang, Xiaomo Li, Punn Augsornworawat, Edward Benjamin Thorp, Evan Alexander Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Atherosclerosis, a leading cause of heart disease, results from chronic vascular inflammation that is driven by diverse immune cell populations. Nanomaterials may function as powerful platforms for diagnostic imaging and controlled delivery of therapeutics to inflammatory cells in atherosclerosis, but efficacy is limited by nonspecific uptake by cells of the mononuclear phagocytes system (MPS). MPS cells located in the liver, spleen, blood, lymph nodes, and kidney remove from circulation the vast majority of intravenously administered nanomaterials regardless of surface functionalization or conjugation of targeting ligands. Here, we report that nanostructure morphology alone can be engineered for selective uptake by dendritic cells (DCs), which are critical mediators of atherosclerotic inflammation. Employing near-infrared fluorescence imaging and flow cytometry as a multimodal approach, we compared organ and cellular level biodistributions of micelles, vesicles (i.e., polymersomes), and filomicelles, all assembled from poly(ethylene glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS) block copolymers with identical surface chemistries. While micelles and filomicelles were respectively found to associate with liver macrophages and blood-resident phagocytes, polymersomes were exceptionally efficient at targeting splenic DCs (up to 85% of plasmacytoid DCs) and demonstrated significantly lower uptake by other cells of the MPS. In a mouse model of atherosclerosis, polymersomes demonstrated superior specificity for DCs (p < 0.005) in atherosclerotic lesions. Furthermore, significant differences in polymersome cellular biodistributions were observed in atherosclerotic compared to naïve mice, including impaired targeting of phagocytes in lymph nodes. These results present avenues for immunotherapies in cardiovascular disease and demonstrate that nanostructure morphology can be tailored to enhance targeting specificity.

Original languageEnglish (US)
Pages (from-to)11290-11303
Number of pages14
JournalACS nano
Volume10
Issue number12
DOIs
StatePublished - Dec 27 2016

Keywords

  • atherosclerosis
  • biodistribution
  • dendritic cells
  • flow cytometry
  • near-infrared fluorescence imaging
  • polymersome
  • targeted delivery

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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