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Polyethylene glycol modified, cross-linked starch-coated iron oxide nanoparticles for enhanced magnetic tumor targeting
Open accessAbstract
While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, potentially enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140-190 nm) and relative PEG labeling (1.5% of surface amines - A5/D5, 0.4% - A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37 °C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 h) and D20 (11.75 h) showing much longer half-lives than D (0.12 h). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC(0-∞). Sustained tumor exposure over 24 h was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that a polyethylene glycol modified, cross-linked starch-coated MNP is a promising platform for enhanced magnetic tumor targeting, warranting further study in tumor models.
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“Molecular weight and surface density of PEG coatings are two critical parameters that influence the dispersion stability, cytotoxicity and blood circulation time of iron oxide nanoparticles [71, 87].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [71]
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Metadata
- Authors
- Cole, A. J., David, A. E., Wang, J., Galbán, C. J., Hill, H. L., & Yang, V. C.
- Affiliations
- University of Michigan (US)
- Fudan University (CN)
- Tianjin University (CN)
- Corresponding author
- Yang, Victor C.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 32
- Issue
- 8
- Pages
- 2183-2193
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3022959
- OpenAlex
- W2029871153
- Cited by
- 308
- References
- 41
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 15 · 2023: 15 · 2022: 14 · 2021: 20 · 2020: 19 · 2019: 25 · 2018: 23 · 2017: 18 · 2016: 25 · 2015: 26 · 2014: 24 · 2013: 35 · 2012: 24
- FWCI
- 9.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NIH) (CA114612, NS066945)
- Hartwell Foundation Biomedical Research Award
- WCU project (R31-2008-000-10103-01)
- NIGMS (GM007767)
- 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 › Nanoplatforms for cancer theranostics
- Keywords
- iron oxide nanoparticles, polyethylene glycol coating, long-circulating nanoparticles, reticuloendothelial system clearance, macrophage uptake, glioma, MRI contrast agents
- MeSH terms
- Animals, Biocompatible Materials, Cell Line, Cross-Linking Reagents, Electron Spin Resonance Spectroscopy, Ferric Compounds, Macrophages, Magnetic Resonance Imaging, Magnetics, Male, Materials Testing, Neoplasms, Particle Size, Polyethylene Glycols, Rats, Inbred F344, Starch, Molecular Structure, Spectroscopy, Fourier Transform Infrared, Mice, Rats, Metal Nanoparticles
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