A Multitheragnostic Nanobubble System to Induce Blood–Brain Barrier Disruption with Magnetically Guided Focused Ultrasound

Huang, Hsin Yang; Liu, Hao Li; Hsu, Po-Hung; Chiang, Chih Sheng; Tsai, Chih Hung; Shang, Huei; Chen, San‐Yuan; Chen, You Yin

doi:10.1002/adma.201403889

Cited by 96 publications

(95 citation statements)

References 35 publications

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“…Few reports have been published regarding the synthesis of MMBs, which are stabilized by a polymeric, [13][14][15][16] lipid 17,18 or silica 19 shell, and the incorporation of magnetic and therapeutic NPs. In these published studies, the shells of MMBs are normally intact, which hinders MB oscillation at low-amplitude driving forces.…”

Section: Preparation Of Mmbsmentioning

confidence: 99%

“…20 As a result, the release of particle cargo relies on the abrupt collapse and accompanying shell disruption of each MB under high-amplitude driving forces of 3-10 bars. 16,18,19 Such rapid and asymmetrical collapse (that is, cavitation) results in high shear flows, microjets and microstreaming 21 that damage surrounding tissues, such as the endothelium. [4][5][6][7] Furthermore, the synchronous burst release of drugs could exceed toxic limits, limiting the clinical application of these MMBs.…”

Section: Preparation Of Mmbsmentioning

confidence: 99%

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Controlled nanoparticle release from stable magnetic microbubble oscillations

Gao

Chan

et al. 2016

NPG Asia Mater

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Magnetic microbubbles (MMBs) are microbubbles (MBs) coated with magnetic nanoparticles (NPs). MMBs not only maintain the acoustic properties of MBs, but also serve as an important contrast agent for magnetic resonance imaging. Such dual-modality functionality makes MMBs particularly useful for a wide range of biomedical applications, such as localized drug/gene delivery. This article reports the ability of MMBs to release their particle cargo on demand under stable oscillation. When stimulated by ultrasound at resonant frequencies, MMBs of 450 nm to 200 μm oscillate in volume and surface modes. Above an oscillation threshold, NPs are released from the MMB shell and can travel hundreds of micrometers from the surface of the bubble. The migration of NPs from MMBs can be described with a force balance model. With this technology, we deliver doxorubicincontaining poly(lactic-co-glycolic acid) particles across a physiological barrier both in vitro and in vivo, with a 18-fold and 5-fold increase in NP delivery to the heart tissue of zebrafish and tumor tissue of mouse, respectively. The penetration of released NPs in tissues is also improved. The ability to remotely control the release of NPs from MMBs suggests opportunities for targeted drug delivery through/into tissues that are not easily diffused through or penetrated. NPG Asia Materials (2016) 8, e260; doi:10.1038/am.2016.37; published online 8 April 2016 INTRODUCTIONTargeted drug delivery and controlled release is the 'holy grail' of nanomedicine. In this regard, one emerging strategy employs a localized stimulus to precisely deposit drug-containing nanoparticles (NPs) at the tissue/organ of interest. The deposited NPs then continuously release drug molecules in a localized and sustained manner. Current strategies trigger the release of NPs from carriers via enzymes, 1 magnetic fields 2 and shear stress. 3 However, these methods are limited to specific organs/tissues, such as blocked blood vessels. A more versatile technology is desired that allows the targeted delivery of NPs to any organ/tissue while maintaining traceability using a non-invasive imaging modality.The present paper reports a strategy toward this end. Magnetic microbubbles (MMBs), the combination of multi-modal contrastenhanced imaging (both magnetic resonance imaging and ultrasound imaging) with targeted drug delivery (magnetic targeting) and controlled release (bubble cavitation) at any site of interest represents an emerging theranostic platform. However, the current formulations of MMBs, stabilized by a polymeric, lipid or silica shell, need a high acoustic energy field to trigger the release through bubble

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Section: Preparation Of Mmbsmentioning

confidence: 99%

Section: Preparation Of Mmbsmentioning

confidence: 99%

Controlled nanoparticle release from stable magnetic microbubble oscillations

Gao

Chan

et al. 2016

NPG Asia Mater

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“…Finally, recent work suggested that sub-micrometer, nanobubbles (as opposed to supramicrometer microbubbles) may have applications for FUS as well. While nanobubbles have lower ultrasound scattering efficiency than microbubbles, they can penetrate disrupted tumor vascular beds, can be more stable than microbubbles, and are also less likely to undergo inertial cavitation and cause micro hemorrhages [28,29,30,31,32]. A study by Huang et al [28] demonstrated that magnetically guidable nanobubbles can disrupt the BBB and serve as a contrast-enhancing agent for ultrasound (US) and MRI, while causing a lower rate of erythrocyte extravasation than their supra-micrometer sizes counterparts or a commercially available, lipid-based microbubble [28].…”

Section: Strategies For Cns Deliverymentioning

confidence: 99%

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

Tosi

Marnell

Chang

et al. 2017

IJMS

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Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

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“…Huang et al recently fabricated a multi-theranostic nanobubble system by synthesizing nanobubbles using mesoporous silica SPION shell nanoparticles loaded with perfluoropentane. They act as Magnetic resonance imaging (MRI)/US dual-modality contrast agent and cause FUS-induced BBB disruption [184]. This multimodal nanoparticle imaging system has the potential to be used along with gene carriers to deliver therapeutic genes across the BBB for the treatment of glioma cancer.…”

Section: Challenges Associated With and Future Directions Of Triggmentioning

confidence: 99%

Trigger-Responsive Gene Transporters for Anticancer Therapy

et al. 2017

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In the current era of gene delivery, trigger-responsive nanoparticles for the delivery of exogenous nucleic acids, such as plasmid DNA (pDNA), mRNA, siRNAs, and miRNAs, to cancer cells have attracted considerable interest. The cationic gene transporters commonly used are typically in the form of polyplexes, lipoplexes or mixtures of both, and their gene transfer efficiency in cancer cells depends on several factors, such as cell binding, intracellular trafficking, buffering capacity for endosomal escape, DNA unpacking, nuclear transportation, cell viability, and DNA protection against nucleases. Some of these factors influence other factors adversely, and therefore, it is of critical importance that these factors are balanced. Recently, with the advancements in contemporary tools and techniques, trigger-responsive nanoparticles with the potential to overcome their intrinsic drawbacks have been developed. This review summarizes the mechanisms and limitations of cationic gene transporters. In addition, it covers various triggers, such as light, enzymes, magnetic fields, and ultrasound (US), used to enhance the gene transfer efficiency of trigger-responsive gene transporters in cancer cells. Furthermore, the challenges associated with and future directions in developing trigger-responsive gene transporters for anticancer therapy are discussed briefly.

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A Multitheragnostic Nanobubble System to Induce Blood–Brain Barrier Disruption with Magnetically Guided Focused Ultrasound

Cited by 96 publications

References 35 publications

Controlled nanoparticle release from stable magnetic microbubble oscillations

Controlled nanoparticle release from stable magnetic microbubble oscillations

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

Trigger-Responsive Gene Transporters for Anticancer Therapy

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