Protein corona and phospholipase activity drive selective accumulation of nanomicelles in atherosclerotic plaques

Nanomedicine. 2018 Apr;14(3):643-650. doi: 10.1016/j.nano.2017.12.021. Epub 2018 Jan 6.

Abstract

ApoB-100 and Phosphatidylcholine-specific phospholipase C (PC-PLC) are important contributors to atherosclerosis development. ApoB-100 is the main structural protein of LDL, being directly associated with atherosclerosis plaque generation. PC-PLC is highly expressed in atherosclerosis lesions and contributes to their progression. We show how phosphatidylcholine-coated nanomicelles can be used for specific characterisation of atherosclerosis plaque. Results show that ApoB-100 in the protein corona of the nanomicelle targets the particles to atherosclerotic areas in apolipoprotein E-/- mice. Furthermore, PC-PLC selectively removes the polar heads from the phospholipid coating of the nanomicelles leading to their accumulation. To fully characterise the behaviour of the nanomicelles, we developed multimodal probes using a nanoemulsion step. Hybrid imaging revealed plaque accumulation of the nanomicelles and colocalisation with PC-PLC expression and ApoB-100 in the plaque. This study shows how protein corona composition and enzyme-driven nanomaterial accumulation can be used for detection of atherosclerosis.

Keywords: ApoB-100; Atherosclerosis; Molecular imaging; Nanomicelles; Phospholipase C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoprotein B-100 / metabolism
  • Apolipoproteins E / physiology*
  • Ferric Compounds / chemistry*
  • Mice
  • Mice, Knockout, ApoE
  • Micelles*
  • Nanocomposites / administration & dosage
  • Nanocomposites / chemistry*
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / pathology
  • Protein Corona / chemistry
  • Protein Corona / metabolism*
  • Type C Phospholipases / chemistry
  • Type C Phospholipases / metabolism*

Substances

  • Apolipoprotein B-100
  • Apolipoproteins E
  • Ferric Compounds
  • Micelles
  • Protein Corona
  • ferric oxide
  • Type C Phospholipases
  • phosphatidylcholine-specific phospholipase C