Abstract |
Mild hyperthermia has been used in combination with polymer therapeutics to further increase delivery to solid tumors and enhance efficacy. An attractive method for generating heat is through non-invasive high intensity focused ultrasound (HIFU). HIFU is often used for ablative therapies and must be adapted to produce uniform mild hyperthermia in a solid tumor. In this work a magnetic resonance imaging guided HIFU (MRgHIFU) controlled feedback system was developed to produce a spatially uniform 43°C heating pattern in a subcutaneous mouse tumor. MRgHIFU was employed to create hyperthermic conditions that enhance macromolecular delivery. Using a mouse model with two subcutaneous tumors, it was demonstrated that MRgHIFU enhanced delivery of both Evans blue dye (EBD) and Gadolinium-chelated N-(2-hydroxypropyl)methacrylamide ( HPMA) copolymers. The EBD accumulation in the heated tumors increased by nearly 2-fold compared to unheated tumors. The Gadolinium-chelated HPMA copolymers also showed significant enhancement in accumulation over control as evaluated through MRI T1-mapping measurements. Results show the potential of HIFU-mediated hyperthermia for enhanced delivery of polymer therapeutics.
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Authors | Nick Frazier, Allison Payne, Joshua de Bever, Christopher Dillon, Apoorva Panda, Nithya Subrahmanyam, Hamidreza Ghandehari |
Journal | Journal of controlled release : official journal of the Controlled Release Society
(J Control Release)
Vol. 241
Pg. 186-193
(11 10 2016)
ISSN: 1873-4995 [Electronic] Netherlands |
PMID | 27686583
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2016 Elsevier B.V. All rights reserved. |
Chemical References |
- Acrylamides
- Macromolecular Substances
- Organometallic Compounds
- Evans Blue
- Gadolinium
- N-(2-hydroxypropyl)methacrylamide
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Topics |
- Acrylamides
(administration & dosage, metabolism)
- Animals
- Drug Delivery Systems
(methods)
- Evans Blue
(administration & dosage, metabolism)
- Gadolinium
(administration & dosage, metabolism)
- High-Intensity Focused Ultrasound Ablation
(methods)
- Hyperthermia, Induced
(methods)
- Macromolecular Substances
(administration & dosage, metabolism)
- Magnetic Resonance Imaging
- Mice, Inbred Strains
- Neoplasms, Experimental
(diagnostic imaging, metabolism)
- Organometallic Compounds
(administration & dosage, metabolism)
- Xenograft Model Antitumor Assays
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