The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.
SPIO-conjugated, doxorubicin-loaded microbubbles for concurrent MRI and focused-ultrasound enhanced brain-tumor drug delivery
Abstract
The blood-brain barrier (BBB) can be temporarily and locally opened by focused ultrasound (FUS) in the presence of circulating microbubbles (MBs). Currently, contrast-enhanced magnetic resonance imaging (CE-MRI) is used to monitor contrast agent leakage to verify BBB-opening and infer drug deposition. However, despite being administered concurrently, MBs, therapeutic agent, and contrast agent have distinct pharmacodynamic behaviors, thus complicating the quantification and optimization of BBB-opening and drug delivery. Here we propose multifunctional MBs loaded with therapeutic agent (doxorubicin; DOX) and conjugated with superparamagnetic iron oxide (SPIO) nanoparticles. These DOX-SPIO-MBs were designed to concurrently open the BBB and perform drug delivery upon FUS exposure, act as dual MRI and ultrasound contrast agent, and allow magnetic targeting (MT) to achieve enhanced drug delivery. We performed burst-tone FUS after injection of DOX-SPIO-MBs, followed by MT with an external magnet attached to the scalp in a rat glioma model. Animals were monitored by T2-weighted MRI and susceptibility weighted imaging and the concentration of SPIO particles was determined by spin-spin relaxivity. We found that DOX-SPIO-MBs were stable and provided significant superparamagnetic/acoustic properties for imaging. BBB-opening and drug delivery were achieved concurrently during the FUS exposure. In addition, MT increased local SPIO deposition in tumor regions by 22.4%. Our findings suggest that DOX-SPIO-MBs with FUS could be an excellent theranostic tool for future image-guided drug delivery to brain tumors.
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“SPION-labeling in combination with MRI (and recently also MPI) has been the method of choice for cell tracking [193, 255].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [255]
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Recent advances in iron oxide nanocrystal technology for medical imaging☆
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Noninvasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits
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Long-term survival with glioblastoma multiforme
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Barua, S., & Mitragotri, S. (2014) · Nano Today · doi:10.1016/j.nantod.2014.04.008 · Cited by 1,288
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
Qian, X., Zheng, Y., & Chen, Y. (2016) · Advanced Materials · doi:10.1002/adma.201602012 · Cited by 888
Huang, P., Qian, X., Chen, Y., Yu, L., Lin, H., Wang, L., Zhu, Y., & Shi, J. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b11846 · Cited by 664
Drug Delivery Systems, CNS Protection, and the Blood Brain Barrier
Upadhyay, R. K. (2014) · BioMed Research International · doi:10.1155/2014/869269 · Cited by 544
“temporarily and locally opened by focused ultrasound in the presence of circulating microbubbles [124].”
Background
Metadata
- Authors
- Fan, C.-H., Ting, C.-Y., Lin, H.-J., Wang, C.-H., Liu, H.-L., Yen, T.-C., & Yeh, C.-K.
- Affiliations
- National Tsing Hua University (TW)
- Chang Gung University (TW)
- Corresponding author
- Liu, Hao-Li
- Yeh, Chih-Kuang
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 34
- Issue
- 14
- Pages
- 3706-3715
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2067444098
- Cited by
- 225
- References
- 36
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 7 · 2023: 9 · 2022: 13 · 2021: 17 · 2020: 11 · 2019: 25 · 2018: 18 · 2017: 24 · 2016: 24 · 2015: 26 · 2014: 26 · 2013: 9
- FWCI
- 15.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Council of Taiwan (100-2218-E-182-001, 101-2627-M-007-001, 101-2221-E-007-035-MY3)
- National Tsing Hua University (102N2050E1)
- Taiwan National Health Research Institutes (NM-101-PP-04)
- Materials Analysis Technology Inc. Corporation
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- superparamagnetic iron oxide nanoparticles, microbubbles, doxorubicin, focused ultrasound, blood-brain barrier opening, brain tumor drug delivery, magnetic targeting, theranostics, image-guided drug delivery, glioma, MRI contrast agents, ultrasound contrast agents, susceptibility-weighted imaging
- MeSH terms
- Animals, Brain Neoplasms, Doxorubicin, Ferric Compounds, Magnetic Resonance Imaging, Male, Drug Delivery Systems, Rats, Sprague-Dawley, Microbubbles, Cell Line, Tumor, Rats
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