Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents
Abstract 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 (...
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| Format: | Article |
| Language: | English |
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BMC
2016-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | http://link.springer.com/article/10.1186/s12951-016-0157-1 |
| _version_ | 1811183827089883136 |
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| author | Rajneesh Chaudhary Kislay Roy Rupinder Kaur Kanwar Ken Walder Jagat Rakesh Kanwar |
| author_facet | Rajneesh Chaudhary Kislay Roy Rupinder Kaur Kanwar Ken Walder Jagat Rakesh Kanwar |
| author_sort | Rajneesh Chaudhary |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-11T13:04:16Z |
| format | Article |
| id | doaj.art-d4edb27903f647f3ae9c82dbd8f948e1 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T13:04:16Z |
| publishDate | 2016-01-01 |
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| series | Journal of Nanobiotechnology |
| spelling | doaj.art-d4edb27903f647f3ae9c82dbd8f948e12022-12-22T04:22:51ZengBMCJournal of Nanobiotechnology1477-31552016-01-0114111710.1186/s12951-016-0157-1Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agentsRajneesh Chaudhary0Kislay Roy1Rupinder Kaur Kanwar2Ken Walder3Jagat Rakesh Kanwar4Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research (C-MMR), Deakin UniversityNanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research (C-MMR), Deakin UniversityNanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research (C-MMR), Deakin UniversityMetabolic Research Unit, School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research (C-MMR), Deakin UniversityNanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR), School of Medicine (SoM), Faculty of Health, Centre for Molecular and Medical Research (C-MMR), Deakin UniversityAbstract 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.http://link.springer.com/article/10.1186/s12951-016-0157-1AtherosclerosisZinc doped ferrite nanoparticlesHeat shock proteinLactoferrinPsammomys obesusMagnetic resonance imaging |
| spellingShingle | Rajneesh Chaudhary Kislay Roy Rupinder Kaur Kanwar Ken Walder Jagat Rakesh Kanwar Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents Journal of Nanobiotechnology Atherosclerosis Zinc doped ferrite nanoparticles Heat shock protein Lactoferrin Psammomys obesus Magnetic resonance imaging |
| title | Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents |
| title_full | Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents |
| title_fullStr | Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents |
| title_full_unstemmed | Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents |
| title_short | Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents |
| title_sort | engineered atherosclerosis specific zinc ferrite nanocomplex based mri contrast agents |
| topic | Atherosclerosis Zinc doped ferrite nanoparticles Heat shock protein Lactoferrin Psammomys obesus Magnetic resonance imaging |
| url | http://link.springer.com/article/10.1186/s12951-016-0157-1 |
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