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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Auxiliary means such as topical hyperthermia, radiotherapy and high intensity focused ultrasound can be used to enhance EPR effect.
“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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- 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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