Superparamagnetic iron oxide nanoparticles encapsulated in biodegradable thermosensitive polymeric micelles: toward a targeted nanomedicine suitable for image-guided drug delivery
Abstract
Superparamagnetic iron oxide nanoparticles (SPIONs) have been receiving great attention lately due to their various biomedical applications, such as in MR imaging and image guided drug delivery. However, their systemic administration still remains a challenge. In this study, the ability of biodegradable thermosensitive polymeric micelles to stably encapsulate hydrophobic oleic-acid-coated SPIONs (diameter 5-10 nm) was investigated, to result in a system fulfilling the requirements for systemic administration. The micelles were composed of amphiphilic, thermosensitive, and biodegradable block copolymers of poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide dilactate] (mPEG-b-p(HPMAm-Lac2)). The encapsulation was performed by addition of one volume of SPIONs in THF to nine volumes of a cold aqueous mPEG-b-p(HPMAm-Lac2) solution (0 degrees C; below the cloud point of the polymer), followed by rapid heating of the resulting mixture to 50 degrees C, to induce micelle formation ("rapid heating" procedure). Dynamic light scattering (DLS) measurements revealed that approximately 200 nm particles (PDI=0.2) were formed, while transmission electron microscopy (TEM) analysis demonstrated that clusters of SPIONs were present in the core of the micelles. A maximum loading of 40% was obtained, while magnetic resonance imaging (MRI) scanning of the samples demonstrated that the SPION-loaded micelles had high r2 and r2* relaxivities. Furthermore, the r2* values were found to be at least 2-fold higher than the r2 values, confirming the clustering of the SPIONs in the micellar core. The particles showed excellent stability under physiological conditions for 7 days, even in the presence of fetal bovine serum. This, together with their ease of preparation and their size of approximately 200 nm, makes these systems highly suitable for image-guided drug delivery.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Iron oxide nanoparticles can be entrapped inside vesicles like liposomes or polymeric micelles.
“Iron oxide nanoparticles can be entrapped inside of vesicles like liposomes [94–97] or polymeric micelles [98–101].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [101]
Cites
Cornell, R. M., & Schwertmann, U. (2003) · Wiley eBooks · doi:10.1002/3527602097 · Cited by 7,906 · see citing works
Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review
Maeda, H., Wu, J., Sawa, T., Matsumura, Y., & Hori, K. (2000) · Journal of Controlled Release · doi:10.1016/s0168-3659(99)00248-5 · Cited by 6,565 · see citing works
Micellization of block copolymers
Riess, G. (2003) · Progress in Polymer Science · doi:10.1016/s0079-6700(03)00015-7 · Cited by 1,953 · see citing works
Neuberger, T., Schöpf, B., Hofmann, H., Hofmann, M., & von Rechenberg, B. (2005) · Journal of Magnetism and Magnetic Materials · doi:10.1016/j.jmmm.2005.01.064 · Cited by 1,727 · see citing works
Recent advances in iron oxide nanocrystal technology for medical imaging☆
Corot, C., Robert, P., Idée, J., & Port, M. (2006) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2006.09.013 · Cited by 1,461 · see citing works
Wang, Y.-X. J., Hussain, S. M., & Krestin, G. P. (2001) · European Radiology · doi:10.1007/s003300100908 · Cited by 1,381 · see citing works
Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems
Nasongkla, N., Bey, E., Ren, J., Ai, H., Khemtong, C., Guthi, J. S., Chin, S.-F., Sherry, A. D., Boothman, D. A., & Gao, J. (2006) · Nano Letters · doi:10.1021/nl061412u · Cited by 1,238 · see citing works
Theory of NMR signal behavior in magnetically inhomogeneous tissues: The static dephasing regime
Yablonskiy, D. A., & Haacke, E. M. (1994) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910320610 · Cited by 1,201 · see citing works
Oleic acid coating on the monodisperse magnetite nanoparticles
Zhang, L., He, R., & Gu, H.-C. (2006) · Applied Surface Science · doi:10.1016/j.apsusc.2006.05.023 · Cited by 994 · see citing works
Iron Oxide Nanoparticles for Sustained Delivery of Anticancer Agents
Jain, T. K., Morales, M. A., Sahoo, S. K., Leslie‐Pelecky, D. L., & Labhasetwar, V. D. (2005) · Molecular Pharmaceutics · doi:10.1021/mp0500014 · Cited by 904 · see citing works
Locoregional cancer treatment with magnetic drug targeting.
Alexiou, C., Arnold, W. J., Klein, R. J., Parak, F., Hulin, P., Bergemann, C., Erhardt, W. D., Wagenpfeil, S., & Lübbe, A. S. (2000) · PubMed · Cited by 863 · see citing works
Biodistribution, Clearance, and Biocompatibility of Iron Oxide Magnetic Nanoparticles in Rats
Jain, T. K., Reddy, M. K., Morales, M. A., Leslie‐Pelecky, D. L., & Labhasetwar, V. D. (2008) · Molecular Pharmaceutics · doi:10.1021/mp7001285 · Cited by 709 · see citing works
Torchilin, V. P. (2000) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(00)00166-4 · Cited by 680 · see citing works
Illés, E., & Tombácz, E. (2005) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2005.08.003 · Cited by 568 · see citing works
Tumour-targeted nanomedicines: principles and practice
Lammers, T., Hennink, W. E., & Storm, G. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604483 · Cited by 542 · see citing works
Self-citationDextran and albumin derivatised iron oxide nanoparticles: influence on fibroblasts in vitro
Berry, C. C., Wells, S., Charles, S. W., & Curtis, A. S. G. (2003) · Biomaterials · doi:10.1016/s0142-9612(03)00237-0 · Cited by 524 · see citing works
Jordan, A., Scholz, R., Wust, P., Schirra, H., Schiestel, T., Schmidt, H., & Felix, R. (1999) · Journal of Magnetism and Magnetic Materials · doi:10.1016/s0304-8853(98)00558-7 · Cited by 521 · see citing works
Protective Coating of Superparamagnetic Iron Oxide Nanoparticles
Kim, D. K., Mikhaylova, M., Zhang, Y., & Muhammed, M. A. (2003) · Chemistry of Materials · doi:10.1021/cm021349j · Cited by 490 · see citing works
Magnetite-loaded polymeric micelles as ultrasensitive magnetic-resonance probes
Ai, H., Flask, C., Weinberg, B., Shuai, X. ‐., Pagel, M. D., Farrell, D., Duerk, J., & Gao, J. (2005) · Advanced Materials · doi:10.1002/adma.200401904 · Cited by 465 · see citing works
de Jong, S. J., Arias, E. R., Rijkers, D. T. S., van Nostrum, C. F., den Bosch, J. J. K.-V., & Hennink, W. E. (2001) · Polymer · doi:10.1016/s0032-3861(00)00646-7 · Cited by 414 · see citing works
Self-citationThermosensitive and biodegradable polymeric micelles for paclitaxel delivery
Soga, O., van Nostrum, C. F., Fens, M., Rijcken, C. J. F., Schiffelers, R. M., Storm, G., & Hennink, W. E. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2004.12.009 · Cited by 319 · see citing works
Rijcken, C. J. F., Snel, C. J., Schiffelers, R. M., van Nostrum, C. F., & Hennink, W. E. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.08.047 · Cited by 278 · see citing works
Self-citationSpectroscopic Characterization of the Surface of Iron Oxide Nanocrystals
Willis, A. L., Turro, N. J., & O'Brien, S. P. (2005) · Chemistry of Materials · doi:10.1021/cm051370v · Cited by 267 · see citing works
Ma, H., Qi, X., Maitani, Y., & Nagai, T. (2006) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2006.10.006 · Cited by 246 · see citing works
Application of the static dephasing regime theory to superparamagnetic iron‐oxide loaded cells
Bowen, C. V., Zhang, X., Saab, G., et al. (2002) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10192 · Cited by 226 · see citing works
Chen, S., Li, Y., Guo, C., Wang, J., Ma, J., Liang, X., Yang, L., & Liu, H. (2007) · Langmuir · doi:10.1021/la702049d · Cited by 194 · see citing works
Synthesis and Characterization of Soluble Iron Oxide−Dendrimer Composites
Strable, E., Bulte, J. W. M., Moskowitz, B. M., Vivekanandan, K., Allen, M., & Douglas, T. (2001) · Chemistry of Materials · doi:10.1021/cm010125i · Cited by 191 · see citing works
Chen, Z. P., Zhang, Y., Zhang, S., Xia, J., Liu, J. W., Xu, K., & Gu, N. (2007) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2007.09.017 · Cited by 174 · see citing works
Narain, R., Gonzales, M., Hoffman, A. S., Stayton, P. S., & Krishnan, K. M. (2007) · Langmuir · doi:10.1021/la700268g · Cited by 144 · see citing works
Physicochemical Characterization of Degradable Thermosensitive Polymeric Micelles
Soga, O., van Nostrum, C. F., Ramzi, A., Visser, T., Soulimani, F., Frederik, P. M., Bomans, P. H. H., & Hennink, W. E. (2004) · Langmuir · doi:10.1021/la048354h · Cited by 143 · see citing works
Self-citationPreparation and characterization of narrow sized (o/w) magnetic emulsion
Montagne, F., Mondain‐Monval, O., Pichot, C., et al. (2002) · Journal of Magnetism and Magnetic Materials · doi:10.1016/s0304-8853(02)00412-2 · Cited by 128 · see citing works
Rijcken, C. J. F., Hofman, J.-W., van Zeeland, F., Hennink, W. E., & van Nostrum, C. F. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.09.002 · Cited by 112 · see citing works
Self-citationKuhlpeter, R., Dahnke, H., Matuszewski, L., ten Persigehl, T., von Wallbrunn, A., Allkemper, T., Heindel, W. L., Schaeffter, T., & Bremer, C. (2007) · Radiology · doi:10.1148/radiol.2451061345 · Cited by 110 · see citing works
Soga, O., van Nostrum, C. F., & Hennink, W. E. (2004) · Biomacromolecules · doi:10.1021/bm049955q · Cited by 109 · see citing works
Self-citationOkassa, L. N., Marchais, H., Douziech-Eyrolles, L., et al. (2007) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2006.12.020 · Cited by 109 · see citing works
Gonzales, M., & Krishnan, K. M. (2006) · Journal of Magnetism and Magnetic Materials · doi:10.1016/j.jmmm.2006.10.1150 · Cited by 96 · see citing works
Neradovic, D., van Steenbergen, M. J., Vansteelant, L., Meijer, Y. J., van Nostrum, C. F., & Hennink, W. E. (2003) · Macromolecules · doi:10.1021/ma034381n · Cited by 95 · see citing works
Self-citationChattopadhyay, P., & Gupta, R. B. (2002) · Industrial & Engineering Chemistry Research · doi:10.1021/ie020205b · Cited by 79 · see citing works
Liang, Y.-Y., Zhang, L., Li, W., et al. (2007) · Colloid & Polymer Science · doi:10.1007/s00396-007-1672-2 · Cited by 79 · see citing works
Gyergyek, S., Huskić, M., Makovec, D., et al. (2007) · Colloids and Surfaces A Physicochemical and Engineering Aspects · doi:10.1016/j.colsurfa.2007.09.035 · Cited by 46 · see citing works
Kubota, N., Tatsumoto, N., Sano, T., & Matsukawa, Y. (2001) · Journal of Applied Polymer Science · doi:10.1002/1097-4628(20010502)80:5 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Wu, W., Wu, Z., Yu, T., Jiang, C., & Kim, W.-S. (2015) · Science and Technology of Advanced Materials · doi:10.1088/1468-6996/16/2/023501 · Cited by 1,574 · see citing works
Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications
Dadfar, S. M., Roemhild, K., Drude, N. I., von Stillfried, S., Knüchel, R., Kiessling, F., & Lammers, T. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.01.005 · Cited by 1,181 · see citing works
Self-citationShiraishi, K., Hamano, M., Ma, H., Kawano, K., Maitani, Y., Aoshi, T., Ishii, K. J., & Yokoyama, M. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2012.11.016 · Cited by 141 · see citing works
Upponi, J. R., Jerajani, K., Nagesha, D. K., Kulkarni, P., Sridhar, S., Ferris, C., & Torchilin, V. P. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.03.054 · Cited by 105 · see citing works
Recent Advances in the Development of Magnetic Nanoparticles for Biomedical Applications
Monteserín, M., Larumbe, S., Martínez, A. V., Burgui, S., & Francisco Martín, L. (2021) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2021.19062 · Cited by 27 · see citing works
- Authors
- Talelli, M., Rijcken, C. J. F., Lammers, T., Seevinck, P. R., Storm, G., van Nostrum, C. F., & Hennink, W. E.
- Affiliations
- Utrecht University (NL)
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Sorbonnelaan 16, P.O. Box 80082, 3508 TB Utrecht, The Netherlands, and Image Sciences Institute, Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, Netherlands
- Corresponding author
- Hennink, Wim E.
- ORCID
- Venue
- Langmuir
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-01-23
- Volume
- 25
- Issue
- 4
- Pages
- 2060-2067
- ISSN
- 0743-7463 (ISSN-L)
- 1520-5827
- OpenAlex
- W1990927888
- Cited by
- 210
- References
- 41
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 8 · 2019: 9 · 2018: 11 · 2017: 11 · 2016: 16 · 2015: 17 · 2014: 18 · 2013: 13 · 2012: 18
- FWCI
- 9.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Langmuir (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Characterization and Applications of Magnetic Nanoparticles
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Keywords
- superparamagnetic iron oxide nanoparticles, biodegradable block copolymers, oleic acid coating, nanoparticle encapsulation, MRI contrast agents, relaxivity, nanoparticle clustering, image-guided drug delivery, systemic administration
- MeSH terms
- Capsules, Ferric Compounds, Hydrogen-Ion Concentration, Magnetics, Micelles, Magnetic Resonance Spectroscopy, Polymers, Molecular Structure, Drug Delivery Systems, Spectroscopy, Fourier Transform Infrared, Microscopy, Electron, Transmission, Nanomedicine, Metal Nanoparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
