Cited by 267Ultrasound and Hyperthermia ApplicationsNanoparticle-Based Drug DeliveryNanoplatforms for cancer theranostics

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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

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Ranjan, Ashish, Jacobs, Genevieve C., Woods, David L., Negussie, Ayele H., Partanen, Ari, Yarmolenko, Pavel S., Gacchina, Carmen E., Sharma, Karun V., Frenkel, Victor, Wood, Bradford J., Dreher, Matthew R.·2012·Journal of Controlled Release

DOI 10.1016/j.jconrel.2011.12.011PMC PMC3319290

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Abstract

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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BackgroundInfluential
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Method
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Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based thermosensitive liposomes
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Method
MRI-Guided Monitoring of Thermal Dose and Targeted Drug Delivery for Cancer Therapy
Fernando, R., Downs, J., Maples, D., & Ranjan, A. (2013) · Pharmaceutical Research · doi:10.1007/s11095-013-1110-8 · Cited by 29
Self and Mutual Radiation Impedances for Modeling of Multi-Frequency CMUT Arrays
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Multifunctional Magnetic Liposomes for Cancer Imaging and Therapeutic Applications
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“According the available in vivo data [18,56,57], the contribution of radiation force in in vivo heat convection and drug release from TSLs has not been established yet.”
Background
MatMRI and MatHIFU: software toolboxes for real-time monitoring and control of MR-guided HIFU
Zaporzan, B., Waspe, A. C., Looi, T., Mougenot, C., Partanen, A., & Pichardo, S. (2013) · Journal of Therapeutic Ultrasound · doi:10.1186/2050-5736-1-7 · Cited by 29
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“For example, a study showed that a greater than 7 fold increase in concentration of anti-cancer doxorubicin was observed in a tumor heated (about 40C) by highintensity focused ultrasound as compared to unsonicated tumors, when rabbits were administered with clinical-grade doxorubicin encapsulated low temperature sensi…”
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Synthesis and characterisation of ultrasound imageable heat-sensitive liposomes for HIFU therapy
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“magnetic resonance image-guided high intensity focused ultrasound (MR-HIFU) resulted in improved drug accumulation and distribution in tumours [6,10].”
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Studies on interaction potency model based on drug synergy and therapeutic potential of triple stimuli-responsive delivery of doxorubicin and 5-fluoro-2-deoxyuridine against lymphoma using disulfide-bridged cysteine over mesoporous silica nanoparticles
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“5fold greater compared with free drugs.(19) Magnetically charged nanoparticles are another strategy employed to treat tumors via drug delivery.”
Background
A Clickable and Photocleavable Lipid Analogue for Cell Membrane Delivery and Release
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Intelligent recognitive systems in nanomedicine
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“6 fold greater concentrations of doxorubicin than freely administered drug while also administering it more evenly through the tumor tissue including the core [44].”
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Image-guided nanomedicine for cancer
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Motion Compensated Ultrasound Imaging Allows Thermometry and Image Guided Drug Delivery Monitoring from Echogenic Liposomes
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“Previously, we and others showed that MR-thermometry provides high spatial and temporal resolution for IGDD of tumors [5, 36, 37], but MR technology is sensitive to tissue motion and to external perturbation of the magnetic field [38].”
Background
Enhanced Delivery of Radiolabeled Polyoxazoline into Tumors via Self-Aggregation under Hyperthermic Conditions
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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.
ORCID: Ranjan, Ashish
Woods, David L.
Negussie, Ayele H.
Partanen, Ari
Frenkel, Victor
Wood, Bradford J.
Venue: Journal of Controlled Release
Publisher: Elsevier BV
Published: 2012-03
Volume: 158
Issue: 3
Pages: 487-494
ISSN: 0168-3659 (ISSN-L)
DOI: 10.1016/j.jconrel.2011.12.011
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Image-guided drug delivery with magnetic resonance guided high intensity focused ultrasound and temperature sensitive liposomes in a rabbit Vx2 tumor model

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