Cited by 225Ultrasound and Hyperthermia ApplicationsNanoparticle-Based Drug DeliveryNanoplatforms for cancer theranostics

SPIO-conjugated, doxorubicin-loaded microbubbles for concurrent MRI and focused-ultrasound enhanced brain-tumor drug delivery

Fan, Ching-Hsiang, Ting, Chien-Yu, Lin, Han-Jung, Wang, Chung-Hsin, Liu, Hao-Li, Yen, Tzu-Chen, Yeh, Chih-Kuang·2013·Biomaterials

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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Crossref · 10.1016/j.biomaterials.2013.01.099

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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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