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Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields
Open accessAbstract
The use of stents for vascular disease has resulted in a paradigm shift with significant improvement in therapeutic outcomes. Polymer-coated drug-eluting stents (DES) have also significantly reduced the incidence of reobstruction post stenting, a disorder termed in-stent restenosis. However, the current DESs lack the capacity for adjustment of the drug dose and release kinetics to the disease status of the treated vessel. We hypothesized that these limitations can be addressed by a strategy combining magnetic targeting via a uniform field-induced magnetization effect and a biocompatible magnetic nanoparticle (MNP) formulation designed for efficient entrapment and delivery of paclitaxel (PTX). Magnetic treatment of cultured arterial smooth muscle cells with PTX-loaded MNPs caused significant cell growth inhibition, which was not observed under nonmagnetic conditions. In agreement with the results of mathematical modeling, significantly higher localization rates of locally delivered MNPs to stented arteries were achieved with uniform-field–controlled targeting compared to nonmagnetic controls in the rat carotid stenting model. The arterial tissue levels of stent-targeted MNPs remained 4- to 10-fold higher in magnetically treated animals vs. control over 5 days post delivery. The enhanced retention of MNPs at target sites due to the uniform field-induced magnetization effect resulted in a significant inhibition of in-stent restenosis with a relatively low dose of MNP-encapsulated PTX (7.5 μg PTX/stent). Thus, this study demonstrates the feasibility of site-specific drug delivery to implanted magnetizable stents by uniform field-controlled targeting of MNPs with efficacy for in-stent restenosis.
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“In a follow-up study using the same experimental setup, the group used magnetic nanoparticles loaded with paclitaxel for local delivery, and they observed a substantial reduction in restenosis with low doses of paclitaxel103.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [103]
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“Chorny et al.(44) used magnetic nanoparticles for the local delivery of paclitaxel.”
Hybrid magnetic iron oxide nanoparticles with tunable field-directed self-assembly
Malik, V., Pal, A., Pravaz, O., Crassous, J. J., Granville, S., Grobéty, B., Hirt, A. M., Dietsch, H., & Schurtenberger, P. (2017) · Nanoscale · doi:10.1039/c7nr04518b · Cited by 32
Son, H. Y., Kim, K. R., Hong, C. A., & Nam, Y. S. (2018) · ACS Omega · doi:10.1021/acsomega.8b00538 · Cited by 32
Hewlin, R. L., Ciero, A., & Kizito, J. P. (2019) · Cardiovascular Engineering and Technology · doi:10.1007/s13239-019-00411-8 · Cited by 32
Cell surface nucleolin as active bait for nanomedicine in cancer therapy: a promising option
Ferrara, B., Belbekhouche, S., Habert, D., Houppe, C., Vallée, B., Bourgoin‐Voillard, S., Cohen, J. L., Cascone, I., & Courty, J. (2021) · Nanotechnology · doi:10.1088/1361-6528/abfb30 · Cited by 32
“…obtaining a target therapy through functionalization with AS1411 aptamer, a hybridized DNA structure was designed by the group of Sun et al [ 93 ] and conjugated with SPIONs to generate a multifunctional nanoformulation carrying a chemotherapeutic drug and a photosensitizer molecule [ 136, 137 ] .”
Recent strategies to design vascular theranostic nanoparticles
Gupta, M. K., Lee, Y., Boire, T. C., Lee, J.-B., Kim, W. S., & Sung, H. (2017) · Nanotheranostics · doi:10.7150/ntno.18531 · Cited by 32
“This approach provided a site-specific drug delivery method to implanted magnetizable stents by uniform magnetic field-controlled targeting of MNPs for the treatment of in-stent restenosis [56].”
MethodMannell, H., Pircher, J., Räthel, T. R., Schilberg, K., Zimmermann, K., Pfeifer, A., Mykhaylyk, O. M., Gleich, B., Pohl, U., & Krötz, F. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0678-8 · Cited by 31
Initiation of Targeted Nanodrug Delivery in Vivo by a Multifunctional Magnetic Implant
Ge, J., Zhang, Y., Dong, Z., Jia, J., Zhu, J., Miao, X., & Yan, B. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b05009 · Cited by 31
Nanoparticles as a Novel Platform for Cardiovascular Disease Diagnosis and Therapy
Tang, C., Zhou, K., Wu, D., & Zhu, H. M. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s474888 · Cited by 32
“83”
Magnetically enhanced cell delivery for accelerating recovery of the endothelium in injured arteries
Adamo, R. F., Fishbein, I., Zhang, K., Wen, J., Levy, R. J., Alferiev, I. S., & Chorny, M. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.12.025 · Cited by 30
“In the context of targeted vascular therapy, this approach has previously been shown effective by our group at localizing small-molecule drugs, gene delivery vectors and xenogeneic cells in injured arteries [24,30,31].”
Self-citationNanotechnology for the treatment of coronary in stent restenosis: a clinical perspective
McDowell, G., SLEVIN, M. A., & Krupiński, J. (2011) · Vascular Cell · doi:10.1186/2045-824x-3-8 · Cited by 30
Ullah, A., Ullah, M., & Lim, S. I. (2024) · Current Problems in Cardiology · doi:10.1016/j.cpcardiol.2024.102396 · Cited by 31
Analysis of Trajectories for Targeting of Magnetic Nanoparticles in Blood Vessels
Heidsieck, A., Vosen, S., Zimmermann, K., Wenzel, D., & Gleich, B. (2012) · Molecular Pharmaceutics · doi:10.1021/mp3001155 · Cited by 29
Zhao, X., Du, P., & Liu, P. (2012) · Molecular Pharmaceutics · doi:10.1021/mp300363g · Cited by 28
Monocyte-mediated drug delivery systems for the treatment of cardiovascular diseases
Aizik, G., Grad, E., & Golomb, G. (2017) · Drug Delivery and Translational Research · doi:10.1007/s13346-017-0431-2 · Cited by 28
Nanoparticles for Detection and Treatment of Peripheral Arterial Disease
Noukeu, L. C., Wolf, J., Yuan, B., Banerjee, S., & Nguyen, K. T. (2018) · Small · doi:10.1002/smll.201800644 · Cited by 28
Magnetofection In Vivo by Nanomagnetic Carriers Systemically Administered into the Bloodstream
Sizikov, A. A., Nikitin, P. I., & Nikitin, M. P. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13111927 · Cited by 33
Magnetic Stents Retain Nanoparticle-Bound Antirestenotic Drugs Transported by Lipid Microbubbles
Räthel, T. R., Mannell, H., Pircher, J., Gleich, B., Pohl, U., & Krötz, F. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0643-y · Cited by 27
“However, the concept of magnetizeable stents has previously been used successfully to deliver nanoparticle loaden cells to stents of 304 stainless steel, too, which were also magnetic, and may not cause these problems (10,11,23).”
Progress and prospects of endothelial progenitor cell therapy in coronary stent implantation
Lan, H., Wang, Y., Yin, T., Wang, Y., Liu, W., Zhang, X., Yu, Q., Wang, Z., & Wang, G. (2015) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.33398 · Cited by 27
“Recently, Chorny et al.(93) reported targeting of endothelial cells loaded with biodegradable magnetic nanoparticles (MNPs) to stented arteries using the magnetizing effect of homogeneous magnetic fields on the susceptible materials, 304-grade stainless steel, and MNP-incorporated magnetite.”
BackgroundInfluentialOptimization of Magnetic Nanoparticle-Assisted Lentiviral Gene Transfer
Trueck, C., Zimmermann, K., Mykhaylyk, O. M., Anton, M., Vosen, S., Wenzel, D., Fleischmann, B. K., & Pfeifer, A. (2012) · Pharmaceutical Research · doi:10.1007/s11095-011-0660-x · Cited by 26
“In combination with magnetizable stents drug coupled MNPs were already successfully applied for local drug delivery (14) as well as MNP loaded endothelial cells for local cell positioning (15).”
Kilgus, C., Heidsieck, A., Ottersbach, A., Roell, W., Trueck, C., Fleischmann, B. K., Gleich, B., & Sasse, P. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0647-7 · Cited by 24
Vascular Nanomedicine: Current Status, Opportunities, and Challenges
Sun, M. T., & Gupta, A. S. (2019) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0039-1692395 · Cited by 24
Applications and Efficacy of Iron Oxide Nanoparticles in the Treatment of Brain Tumors
Varalli, L., Berlet, R., Abenojar, E., McDaid, J., Gascoigne, D. A., Bailes, J., & Aksenov, D. P. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17040499 · Cited by 23
“Such a strategy has shown promise in other fields, including using magnetic stents to attract Such a strategy has shown promise in other fi elds, including using magnetic stents to a tt ract therapeutic nanoparticles [177–181].”
Chorny, M., Alferiev, I. S., Fishbein, I., Tengood, J. E., Folchman-Wagner, Z., Forbes, S. P., & Levy, R. J. (2012) · Pharmaceutical Research · doi:10.1007/s11095-012-0675-y · Cited by 23
“using a modification of the emulsification-solvent evaporation approach (16) from fully biodegradable components, including PLA as the matrix-forming material, nanocrystal-”
MethodSelf-citation
Metadata
- Authors
- Chorny, M., Fishbein, I., Yellen, B. B., Alferiev, I. S., Bakay, M., Ganta, S., Adamo, R., Amiji, M., Friedman, G., & Levy, R. J.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Duke University (US)
- Northeastern University (US)
- Drexel University (US)
- Corresponding author
- Levy, Robert J.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-04-19
- Volume
- 107
- Issue
- 18
- Pages
- 8346-8351
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2889533
- OpenAlex
- W2154590970
- Cited by
- 197
- References
- 30
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 9 · 2021: 12 · 2020: 6 · 2019: 10 · 2018: 13 · 2017: 17 · 2016: 18 · 2015: 8 · 2014: 20 · 2013: 16 · 2012: 21
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Children's Hospital of Philadelphia
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007915)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- drug-eluting stents, paclitaxel, magnetic nanoparticles, magnetic targeting, uniform magnetic field, in-stent restenosis, local drug delivery, arterial smooth muscle cells, carotid artery stenting, nanoparticle retention, vascular disease
- MeSH terms
- Animals, Cell Line, Graft Occlusion, Vascular, Magnetics, Male, Stents, Drug Delivery Systems, Rats, Sprague-Dawley, Paclitaxel, Microscopy, Electron, Transmission, Cell Proliferation, Rats, Metal Nanoparticles
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