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Macrophage-targeted and clearable glutathione-based MRI nanoprobes for atherosclerosis molecular imaging

  • Liang Li
  • Jiahui Wang
  • Menglin Wu
  • Yana He
  • Hongtuan Zhang
  • Guoping Xu
  • Li Chen
  • Xinying Jia
  • Qi Guo
  • Xuening ZhangEmail author
Research Paper
  • 10 Downloads

Abstract

Foam macrophage infiltration is one of the clinical features of high-risk atherosclerotic plaques. Many imaging modalities such as magnetic resonance imaging (MRI) have been used to detect foam macrophages for evaluating plaque vulnerability. However, targeting efficiency, biocompatibility, and clearance remain pivotal challenges in design of new MRI contrast agents. Herein, we report a sensitive, class AI scavenger receptors (SR-AI)-targeted, glutathione-biomineralized gadolinium-based nanoparticle for noninvasive precise MR imaging of macrophages within carotid atherosclerotic lesions in apoE-deficient (ApoE−/−) mice. The resultant PP1 (16-mer peptide, LSLERFLRCWSDAPAK)-gold-gadolinium nanoparticles (NPs) possessed superior stability, prominent longitudinal relaxivity, and negligible cytotoxicity. In vitro results showed the highest internalization in activated macrophages and in vivo MR images revealed signal augment in carotid atherosclerotic lesions after PP1-gold-gadolinium NP administration at 4 h and 12 h, which were strong testimonial to the formidable macrophage-targeting ability and the subsequent atherosclerosis-retention biofunctions. To summarize, our tactically elaborated biocompatible multifunctional MR NPs integrate T1 signal amplification, precise macrophage targeting, and systematic clearance capabilities, which offer an innovative strategy for noninvasively characterizing vulnerable plaques of early-stage atherosclerosis, or for a wide range of clinical diagnosis and treatment applications.

Keywords

Clearable nanoparticles Macrophage targeting MRI Atherosclerosis Nanomedicine 

Notes

Funding

This study was funded by the National Natural Science Foundation of China (81701826), Key Project of Tianjin Natural Science Foundation (16KPXMSF00140), Key Project of Tianjin Health and Family Planning Commission (16KG115), and Science Foundation of the Second Hospital of Tianjin Medical University (2017YDEY11, 2018YDEY11).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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11051_2019_4688_MOESM2_ESM.docx (2.7 mb)
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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of RadiologyThe Second Hospital of Tianjin Medical UniversityTianjinPeople’s Republic of China
  2. 2.Department of Medical ImagingThe First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjinPeople’s Republic of China
  3. 3.Department of UrologyThe Second Hospital of Tianjin Medical University, Sex Hormone Research Center, Tianjin Institute of UrologyTianjinPeople’s Republic of China
  4. 4.Department of UltrasonographyTianjin Medical University General HospitalTianjinPeople’s Republic of China

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