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Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents

Chaudhary, Rajneesh, Roy, Kislay, Kanwar, Rupinder Kaur, Walder, Ken and Kanwar, Jagat Rakesh 2016, Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents, Journal of nanobiotechnology, vol. 14, no. Article number : 6, pp. 1-17, doi: 10.1186/s12951-016-0157-1.

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Title Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents
Author(s) Chaudhary, Rajneesh
Roy, Kislay
Kanwar, Rupinder Kaur
Walder, Ken
Kanwar, Jagat Rakesh
Journal name Journal of nanobiotechnology
Volume number 14
Issue number Article number : 6
Start page 1
End page 17
Total pages 17
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2016
ISSN 1477-3155
Keyword(s) atherosclerosis
zinc doped ferrite nanoparticles
heat shock protein
lactoferrin
psammomys obesus
magnetic resonance imaging
Summary BACKGROUND: Cardiovascular diseases are the most prevalent cause of morbidity and mortality affecting millions of people globally. The most effective way to counter cardiovascular complications is early diagnosis and the safest non-invasive diagnostic approach is magnetic resonance imaging (MRI). In this study, superparamagnetic ferrite nanoparticles doped with zinc, exhibiting highly enhanced saturation magnetization and T2 and computed tomography (CT) contrast were synthesized. These nanoparticles have been strategically engineered using bovine lactoferrin (Lf), polyethylene glycol (PEG), and heat shock protein (Hsp)-70 antibody specifically targeting atherosclerosis with potential therapeutic value. The nanocomplexes were further validated in vitro to assess their cytotoxicity, internalization efficiency, effects on cellular proliferation and were assessed for MRI as well as X-ray CT in ex vivo Psammomys obesus rat model.

RESULTS: Optimized zinc doped ferrite nanoparticles (Zn0.4Fe2.6O4) with enhanced value of maximum saturation magnetization value on 108.4 emu/g and an average diameter of 24 ± 2 nm were successfully synthesized. Successfully incorporation with bovine lactoferrin, PEG and Hsp-70 (70 kDa) antibody led to synthesis of spherical nanocomplexes (size 224.8 nm, PDI 0.398). A significantly higher enhancement in T2 (p < 0.05, 1.22-fold) and slightly higher T1 (1.09-fold) and CT (1.08-fold) contrast compared to commercial ferrite nanoparticles was observed. The nanocomplexes exhibited effective cellular internalization within 2 h in both THP-1 and Jurkat cells. MRI scans of contrast agent injected animal revealed significant arterial narrowing and a significantly higher T2 (p < 0.05, 1.71-fold) contrast in adult animals when compared to juvenile and control animals. The excised heart and aorta agar phantoms exhibited weak MRI contrast enhancement in juvenile animal but significant contrast enhancement in adult animal specifically at the aortic arch, descending thoracic aorta and iliac bifurcation region with X-ray CT scan. Histological investigation of the contrast agent injected aorta and heart confirmed site target-specific accumulation at the atherosclerotic aortic arch and descending thoracic aorta of the adult animal with severely damaged intima full of ruptured microatheromas.

CONCLUSION: Overall, the study demonstrates the strategic development of nanocomplex based bimodal MRI and CT contrast agents and its validation on Psammomys obesus for atherosclerosis diagnostics.
Language eng
DOI 10.1186/s12951-016-0157-1
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30081881

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.