Controllable in vivo hyperthermia effect induced by pulsed high intensity focused ultrasound with low duty cycles

Tu, Juan; Hwang, Joo Ha; Chen, Tao; Fan, Tingbo; Guo, Xiaojun; Crum, Lawrence A.; Zhang, Dong

doi:10.1063/1.4754113

Cited by 25 publications

(12 citation statements)

References 18 publications

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“…Focused Ultrasound (FUS) induces deep and localised hyperthermia in a controlled manner when MR thermometry is used [21]. Its application to enhance accumulation of nanoparticles in tumours and/or induce drug release from carriers, has been studied during the last years.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours

Centelles

Wright

et al. 2018

Journal of Controlled Release

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Image guided drug delivery using imageable thermosensitive liposomes (iTSLs) and high intensity focused ultrasound (FUS or HIFU) has attracted interest as a novel and non-invasive route to targeted delivery of anti-cancer therapeutics. FUS-induced hyperthermia is used as an externally applied "trigger" for the release of a drug cargo from within thermosensitive drug carriers. It is suggested that sub-ablative hyperthermia significantly modifies the permeability of tumour vasculature and enhances nanoparticle uptake. Here we describe the preparation and use of magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF) labelled thermosensitive liposomes for imaging and tracking of biodistribution and drug release in a murine cancer model. We prepared iTSLs to encapsulate topotecan (Hycamtin®), a chemotherapeutic agent which when released in tumours can be monitored by an increase in its intrinsic drug fluorescence. FUS was applied using feedback via subcutaneously placed fine-wire thermocouples to maintain and monitor hyperthermic temperatures. iTSL accumulation was detected within tumours using NIRF imaging immediately after liposome administration. Mild FUS-induced hyperthermia (3 min at 42 °C, 30 min post i.v. administration) greatly enhanced iTSLs uptake. A co-localised enhancement of topotecan fluorescence emission was also observed immediately after application of FUS indicating rapid triggered drug release. The phenomena of increased iTSL accumulation and concomitant topotecan release appeared to be amplified by a second mild hyperthermia treatment applied one hour after the first. MRI in vivo also confirmed enhanced iTSLs uptake due to the FUS treatments. Our imaging results indicate the effects of hyperthermia on the uptake of carriers and drug. FUS-induced hyperthermia combined with real time imaging could be used as a tool for tumour targeted drug delivery.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours

Centelles

Wright

et al. 2018

Journal of Controlled Release

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“…Using microwave radio frequency, high intensity focused ultrasound (HIFU) or ultrasound, we can easily achieve an adequate temperature for heat-induced siRNA expression in extremities, ovary, brain, breast, prostate, head and neck. 26 Indeed, a precise temporal and spatially controlled target gene expression system in vivo has been established using MRI-guided focused ultrasound (MRI-FUS) for hyperthermia and HSP70 promoter activation with a realtime feedback control on a whole-body clinical MRI system. 28,53 This controllable gene expression system can also be used in siRNA expression with our heat-inducible siRNA cassette.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, extensive technological development over the last decade has significantly improved the ability to heat more target areas in the body. Using microwave radio frequency, high intensity focused ultrasound (HIFU) or ultrasound, we can easily achieve an adequate temperature for heat‐induced siRNA expression in extremities, ovary, brain, breast, prostate, head and neck . Indeed, a precise temporal and spatially controlled target gene expression system in vivo has been established using MRI‐guided focused ultrasound (MRI‐FUS) for hyperthermia and HSP70 promoter activation with a real‐time feedback control on a whole‐body clinical MRI system .…”

Section: Discussionmentioning

confidence: 99%

“…To address this problem, we attempt to regulate the siRNA expression using heat response elements (HSE). On the one hand, in tumor targeted therapy, hyperthermia is an effective way to eradicate tumor cells via microwave radio frequency, high intensity focused ultrasound (HIFU), or ultrasound increasing local lesion temperature . Meanwhile, hyperthermia has the advantages of accurate positioning and no side effects.…”

Section: Introductionmentioning

confidence: 99%

“…effective way to eradicate tumor cells via microwave radio frequency, high intensity focused ultrasound (HIFU), or ultrasound increasing local lesion temperature. [26][27][28] Meanwhile, hyperthermia has the advantages of accurate positioning and no side effects. On the other hand, the human HSP70 promoter is able to achieve a temperature-activated gene expression, which would be useful in clinical applications.…”

Section: Introductionmentioning

confidence: 99%

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A siRNA system based on HSP70 promoter results in controllable and powerful gene silencing by heat‐induction

Liao

Feng

Qian

et al. 2013

Biotechnology Progress

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RNAi is a powerful tool for gene-specific knockdown and gene therapy. However, the imprecise expression of siRNA limits the extensive application of RNAi in gene therapy. Here we report the development of a novel controllable siRNA expression vector pMHSP70psil that is initiated by HSP70 promoter. We determined the efficiency of the controllable siRNA system by targeting the gama-synuclein (SNCG) gene in breast cancer cells MCF-7. The results show that the controllable siRNA system can be induced to initiate siRNA expression by heat-induction. The silencing effect of SNCG occurs at a relatively low level (10.1%) at 37°C, while it is significantly increased to 69.4% after heat induction at 43°C. The results also show that the controllable siRNA system inhibits proliferation of cancer cells by heat-shock. Therefore, this RNAi strategy holds the promise of the high efficiency in gene knockdown at targeted times and locations, avoiding systemic side effects. It provides, for the first time, an approach to control siRNA expression by heat-shock.

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A Mitochondrion‐Targeting Piezoelectric Nanosystem for the Treatment of Erectile Dysfunction via Autophagy Regulation

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Advanced Materials

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Mitochondrial damage caused by external stimuli, such as high glucose levels and inflammation, results in excessive reactive oxygen species (ROS) production. Existing antioxidants can only scavenge ROS and cannot address the root cause of ROS production, namely, abnormal mitochondria. To overcome this limitation, the study develops a piezoelectric synergistic drug‐loaded nanosystem (BaTCG nanosystem) that targets mitochondria. The BaTCG nanosystem is delivered to mitochondria via triphenylphosphine modification, and generates current under the stimulation of ultrasound, thereby promoting mitochondrial autophagy and restoring mitochondrial homeostasis. In a model of diabetes‐related erectile dysfunction (ED), the BaTCG nanosystem, through the current induced by the piezoelectric effect, not only promoted mitophagy, thereby reducing ROS production, but also released long‐acting glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) to effectively reduce blood glucose levels and mitochondrial damage. Each component of this nanosystem functions individually as well as synergistically, thus facilitating corpus cavernosum repair and restoring erectile function. In conclusion, the findings offer a novel therapeutic strategy for diabetes‐related ED and a target for the treatment of diabetes‐related conditions with functionalized nanoparticles to regulate mitophagy.

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Controllable in vivo hyperthermia effect induced by pulsed high intensity focused ultrasound with low duty cycles

Cited by 25 publications

References 18 publications

Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours

Image-guided thermosensitive liposomes for focused ultrasound drug delivery: Using NIRF-labelled lipids and topotecan to visualise the effects of hyperthermia in tumours

A siRNA system based on HSP70 promoter results in controllable and powerful gene silencing by heat‐induction

A Mitochondrion‐Targeting Piezoelectric Nanosystem for the Treatment of Erectile Dysfunction via Autophagy Regulation

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