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Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model
Open accessAbstract
Clinical-grade doxorubicin encapsulated low temperature sensitive liposomes (LTSLs) were combined with a clinical magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) platform to investigate in vivo image-guided drug delivery. Plasma pharmacokinetics were determined in 3 rabbits. Fifteen rabbits with Vx2 tumors within superficial thigh muscle were randomly assigned into three treatment groups: 1) free doxorubicin, 2) LTSL and 3) LTSL + MR-HIFU. For the LTSL + MR-HIFU group, mild hyperthermia (40-41 °C) was applied to the tumors using an MR-HIFU system. Image-guided non-invasive hyperthermia was applied for a total of 30 min, completed within 1h after LTSL infusion. High-pressure liquid chromatography (HPLC) analysis of the harvested tumor and organ/tissue homogenates was performed to determine doxorubicin concentration. Fluorescence microscopy was performed to determine doxorubicin spatial distribution in the tumors. Sonication of Vx2 tumors resulted in accurate (mean = 40.5 ± 0.1 °C) and spatially homogenous (SD = 1.0 °C) temperature control in the target region. LTSL + MR-HIFU resulted in significantly higher tumor doxorubicin concentrations (7.6- and 3.4-fold greater compared to free doxorubicin and LTSL respectively, p<0.05, Newman-Keuls). This improved tumor concentration was achieved despite heating <25% of the tumor volume. Free doxorubicin and LTSL treatments appeared to deliver more drug in the tumor periphery as compared to the tumor core. In contrast, LTSL + MR-HIFU treatment suggested an improved distribution with doxorubicin found in both the tumor periphery and core. Doxorubicin bio-distribution in non-tumor organs/tissues was fairly similar between treatment groups. This technique has potential for clinical translation as an image-guided method to deliver drug to a solid tumor.
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“Some auxiliary means, such as topical hyperthermia, radiotherapy and high intensity focused ultrasound, etc., can also be used to enhance this effect [158–160].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [160]
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Metadata
- Authors
- Ranjan, A., Jacobs, G. C., Woods, D. L., Negussie, A. H., Partanen, A., Yarmolenko, P. S., Gacchina, C. E., Sharma, K. V., Frenkel, V., Wood, B. J., & Dreher, M. R.
- Affiliations
- National Institutes of Health (US)
- Catholic University of America (US)
- Corresponding author
- Dreher, Matthew R.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 158
- Issue
- 3
- Pages
- 487-494
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC3319290
- OpenAlex
- W1982194007
- Cited by
- 267
- References
- 44
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 11 · 2023: 14 · 2022: 12 · 2021: 17 · 2020: 12 · 2019: 15 · 2018: 18 · 2017: 20 · 2016: 38 · 2015: 28 · 2014: 30 · 2013: 30 · 2012: 13
- FWCI
- 13.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Center for Interventional Oncology in the Intramural Research Program of the National Institutes of Health
- 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
- image-guided drug delivery, MR-guided focused ultrasound, thermosensitive liposomes, doxorubicin, cancer hyperthermia, VX2 tumor model, plasma pharmacokinetics, drug biodistribution
- MeSH terms
- Animals, Doxorubicin, Female, Liposomes, Neoplasms, Magnetic Resonance Spectroscopy, Rabbits, Temperature, Tissue Distribution, Ultrasonography, Drug Delivery Systems, High-Intensity Focused Ultrasound Ablation
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