High intensity focused ultrasound hyperthermia for enhanced macromolecular delivery

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• 作者：Nick Frazier^a ; ^b ; Allison Payne^c ; Joshua de Bever^c ; Christopher Dillon^c ; Apoorva Panda^b ; ^d ; Nithya Subrahmanyam^b ; ^d ; Hamidreza Ghandehari^a ; ^b ; ^d ; ^{hamid.ghandehari@pharm.utah.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：(AIBN) ; Azobisisobutyronitrile ; (APMA-DOTA) ; aminopropylmethacrylamide-1 ; 4 ; 7 ; 10-tetraazacyclododecane-1 ; 4 ; 7 ; 10-tetraacetic acid ; (DI) ; deionized ; (EBD) ; Evans blue dye ; (EDTA) ; ethylenediaminetetraacetic acid ; (EPR) ; enhanced permeability and retention ; (FDA) ; Food and Drug Administration ; (Gd) ; Gadolinium ; (GNR) ; gold nanorod ; (GRP78) ; glucose regulated protein-78 ; (HIFU) ; high intensity focused ultrasound ; (HPMA) ; N-(2-hydroxypropyl)methacrylamide ; (ICP-MS) ; inductively coupled plasma mass spe
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 November 2016
• 年：2016
• 卷：241
• 期：Complete
• 页码：186-193
• 全文大小：1222 K

文摘

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.