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]
Citations
Cites
The 2007 WHO Classification of Tumours of the Central Nervous System
Louis, D. N., Ohgaki, H., Wiestler, O. D., Cavenee, W. K., Burger, P. C., Jouvet, A., Scheithauer, B. W., & Kleihues, P. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0243-4 · Cited by 15,675
Wen, P. Y., & Kesari, S. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0708126 · Cited by 3,511
Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging
Omid Veiseh, A., Gunn, J., & Zhang, M. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.11.002 · Cited by 1,854
Inorganic Nanoparticles for MRI Contrast Agents
Na, H. B., Song, I. C., & Hyeon, T. (2009) · Advanced Materials · doi:10.1002/adma.200802366 · Cited by 1,811
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 1,498
Noninvasive MR Imaging–guided Focal Opening of the Blood-Brain Barrier in Rabbits
Hynynen, K., McDannold, N. J., Vykhodtseva, N. I., & Jolesz, F. A. (2001) · Radiology · doi:10.1148/radiol.2202001804 · Cited by 1,463
Long-term survival with glioblastoma multiforme
Krex, D., Klink, B., Hartmann, C. J., von Deimling, A., Pietsch, T., Simon, M., Sabel, M., Steinbach, J. P., Heese, O., Reifenberger, G., et al. (2007) · Brain · doi:10.1093/brain/awm204 · Cited by 905
Chertok, B., Moffat, B. A., David, A. E., Yu, F., Bergemann, C., Ross, B. D., & Yang, V. C.-M. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.08.050 · Cited by 901
Hynynen, K., McDannold, N., Sheikov, N. A., Jolesz, F. A., & Vykhodtseva, N. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2004.06.046 · Cited by 679
Sheikov, N. A., McDannold, N. J., Vykhodtseva, N. I., Jolesz, F. A., & Hynynen, K. (2004) · Ultrasound in Medicine & Biology · doi:10.1016/j.ultrasmedbio.2004.04.010 · Cited by 619
Cited by
Sorted by citations
Items 201–225 of 225
Advancement in phase-transitional ultrasound molecular probe
Xu, J., Wang, Z., & Zheng, Y. (2015) · Chinese Science Bulletin (Chinese Version) · doi:10.1360/n972015-00611 · Cited by 1
Micro/Nanobubbles Driven Multimodal Imaging and Theragnostics of Cancer
Zhang, B. X., & Dai, P. Z. (2021) · Advanced ultrasound in diagnosis and therapy · doi:10.37015/audt.2021.200053 · Cited by 1
“The designed multifunctional MBs loaded with DOX and conjugated with SPIO nanoparticles (DOX-SPIO-MBs) exhibited good contrast enhancement in both US and MR imaging [69].”
MethodTheranostic nanoagents: Future of personalized nanomedicine
Sabale, V., Dubey, S., & Sabale, P. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-89839-3.00017-8 · Cited by 1
Evaluating the toxic oral doses of iron oxide nanoparticles in mice
Abawy, N. A., & Al-Zubaidy, M. H. I. (2023) · Al-mağallaẗ al-ʻirāqiyyaẗ li-l-ʻulūm al-bayṭariyyaẗ/Iraqi journal of veterinary sciences · doi:10.33899/ijvs.2023.138368.2796 · Cited by 3
“Histological section of liver of 75mg/ kg after 14 days of treatment, mild vacuolar degeneration of hepatocytes, congestion of central vein, infiltration of inflammatory cells and increase in number of kupffer cells (Figure 5).”
BackgroundAminooxy reagents in nanomedicine and bioanalysis.
Mattingly, S. J. (2014) · doi:10.18297/etd/1751 · Cited by 1
Janagam, D. R. (2017) · doi:10.21007/etd.cghs.2017.0429 · Cited by 1
“inorganic nanoparticles: nanosized inorganic core including gold [322], mesoporous silica [323-325] and SPIO [326, 327], coated with polymers and conjugated with targeting and imaging agents on the surface [344, 345].”
BackgroundAn Ultrasound Contrast Agent Microbubble in a Microvessel: A Numerical Approach
khah, N. H. (2015) · TSpace (University of Toronto) · Cited by 1
Ultrasound-mediated gene delivery by using folic acid-modified cationic microbubbles
Chang, E.-L., Ting, C.-Y., & Yeh, C. (2014) · IEEE International Ultrasonics Symposium · doi:10.1109/ultsym.2014.0257
“Despite the surgery removal, traditional chemotherapy or radiation therapy, the mean life time of patients with glioma remains 1-2 years [1, 2].”
BackgroundTing, C.-Y., Fan, C., Lin, W.-H., Chai, W., Liu, H.-L., Yen, T., & Yeh, C. (2013) · IEEE International Ultrasonics Symposium · doi:10.1109/ultsym.2013.0533
Fan, C., Cheng, Y., Ting, C.-Y., Ho, Y.-J., Hsu, P., Liu, H.-L., & Yeh, C. (2016) · IEEE International Ultrasonics Symposium · doi:10.1109/ultsym.2016.7728533
Ultrasound-responsive nanosystems
Shah, M. R., Imran, M. A., & Ullah, S. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-52729-3.00007-x
Local Treatment of Brain Tumors and the Blood-Brain Barrier
Rajsiglová, L., & Vannucci, L. E. (2018) · Springer eBooks · doi:10.1007/978-3-319-75007-1_7
Molecular Imaging in Diagnosis and Treatment of Brain Tumours
Farrer, N. J., Evans, R. J., Morse, S. V., & Long, N. J. (2022) · Royal Society of Chemistry eBooks · doi:10.1039/9781782624028-00207
McMahon, D., & Hynynen, K. (2022) · AAPS advances in the pharmaceutical sciences series · doi:10.1007/978-3-030-88773-5_19
Ye, X., Shao, B., Jiang, X., Li, J., Liu, X., Chen, X., Cui, Y., Zhang, C., Cen, J., & He, N. (2024) · Chemical Engineering Journal · doi:10.1016/j.cej.2024.153966
Drug delivery to brain: Formulation challenges and potential approaches
Kumari, M., Kumar, A., & Baldi, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13474-6.00027-5
He, C., Wu, Z., Zhuang, M., Li, X., Xue, S., Xu, S., Xu, J., Wu, Z., & Lu, M. (2023) · Figshare · doi:10.6084/m9.figshare.24037333
Recent Advances in Nanotheranostics-Based Personalized Medicine
Patra, P., Mohapatra, D., PANDA, N., Jena, G. K., & Sahoo, R. K. (2025) · Springer eBooks · doi:10.1007/978-981-95-3746-4_16
Anti-breast cancer effects of free and nanocarrier-loaded salinomycin and doxorubicin
Zohreh, A., Moghadam, M. F., Hashemi, Z. S., Sadeghizadeh, M., & Razi, A. (2025) · Advances in Cancer Biology - Metastasis · doi:10.1016/j.adcanc.2025.100168
Preclinical Studies on Stimuli-Responsive Nanosystems for Cancer Therapy
Pasupuleti, V., Kanchumurthy, S., & Khatri, D. K. (2026) · Springer eBooks · doi:10.1007/978-981-95-2744-1_14
Focused ultrasound for brain metastases
Ozair, A., Moiz, B., Anastasiadis, P., Gandhi, D., Amatya, B., McDermott, M. W., Woodworth, G. F., & Ahluwalia, M. S. (2025) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaf131
Saini, I., Nayak, J., Prajapati, K. S., Kumar, S., & Kumar, R. (2026) · ChemistrySelect · doi:10.1002/slct.202507355
Attenuation of DOX‐Associated Biochemical and Histological Brain Alterations
Abdelhiee, E. Y., Fadl, S. E., Elsayed, F., Soliman, A. M., Aboubakr, M., Altalhi, R., Anajirih, N., Majrashi, M., Algahtani, M., Abdel‐Daim, M. M., et al. (2026) · Veterinary Medicine and Science · doi:10.1002/vms3.71161
“ROS may damage proteins, lipids and DNA within cells, resulting in cell death (Fan et al. 2013 ; Moruno-Manchon et al. 2018 ).”
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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