Nanobubble-mediated cancer cell sonoporation using low-frequency ultrasound

Bismuth, Mike; Eck, Michal; Ilovitsh, Tali

doi:10.1039/d3nr03226d

Cited by 4 publications

(4 citation statements)

References 67 publications

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“…However, a recent study has reported that NBs disappear with convergent ultrasound at a low frequency of 80 kHz, which is below the MI 1.9 [39]. Moreover, the combination of NBs and LoFreqUS at 250 kHz with peak negative pressures of 300-500 kPa has been reported to enhance the intracellular delivery of small molecular compounds and effectively reduce the viability of cultured tumor cells [40]. Alternatively, targeted NBs and LoFreqUS have been reported to enhance siRNA delivery into hepatocellular carcinoma cells [41].…”

Section: Discussionmentioning

confidence: 97%

Intracranial Gene Delivery Mediated by Albumin-Based Nanobubbles and Low-Frequency Ultrasound

Koga,

Kida,

Yamasaki

et al. 2024

Nanomaterials

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Research in the field of high-intensity focused ultrasound (HIFU) for intracranial gene therapy has greatly progressed over the years. However, limitations of conventional HIFU still remain. That is, genes are required to cross the blood-brain barrier (BBB) in order to reach the neurological disordered lesion. In this study, we introduce a novel direct intracranial gene delivery method, bypassing the BBB using human serum albumin-based nanobubbles (NBs) injected through a less invasive intrathecal route via lumbar puncture, followed by intracranial irradiation with low-frequency ultrasound (LoFreqUS). Focusing on both plasmid DNA (pDNA) and messenger RNA (mRNA), our approach utilizes LoFreqUS for deeper tissue acoustic penetration and enhancing gene transfer efficiency. This drug delivery method could be dubbed as the “Spinal Back-Door Approach”, an alternative to the “front door” BBB opening method. Experiments showed that NBs effectively responded to LoFreqUS, significantly improving gene transfer in vitro using U-87 MG cell lines. In vivo experiments in mice demonstrated significantly increased gene expression with pDNA; however, we were unable to obtain conclusive results using mRNA. This novel technique, combining albumin-based NBs and LoFreqUS offers a promising, efficient, targeted, and non-invasive solution for central nervous system gene therapy, potentially transforming the treatment landscape for neurological disorders.

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Section: Discussionmentioning

confidence: 97%

Intracranial Gene Delivery Mediated by Albumin-Based Nanobubbles and Low-Frequency Ultrasound

Koga,

Kida,

Yamasaki

et al. 2024

Nanomaterials

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“…The particle size is approximately 600 nm. In recent years, mesoporous silica nanoparticles with large surface areas, large pore volumes, and unique mesoporous structure have been widely used in nanoparticle synergistic therapy. , The CDF-MHMSN as ultrasound contrast agents has better stability and smaller particle size compared to traditional organic microbubbles (usually in micrometer range). , The endothelial gap junction defects in tumor blood vessels is usually 200–800 nm. , The CDF-MHMSN can enter tumor tissues through the endothelial gap junction defects, which overcomes the limitation of traditional organic contrast agents that only realize blood flow and vasculature imaging due to their large size. , In addition, the enormous hollow structure of CDF-MHMSN can provide the contrast-enhanced ultrasound imaging . Cur and Dox are encapsulated inside HMSN to achieve the combination of sonodynamic therapy and chemotherapy, thereby enhancing the efficacy of tumor treatment.…”

Section: Introductionmentioning

confidence: 99%

“…36,37 The CDF-MHMSN can enter tumor tissues through the endothelial gap junction defects, which overcomes the limitation of traditional organic contrast agents that only realize blood flow and vasculature imaging due to their large size. 9,38 In addition, the enormous hollow structure of CDF-MHMSN can provide the contrast-enhanced ultrasound imaging. 39 Cur and Dox are encapsulated inside HMSN to achieve the combination of sonodynamic therapy and chemotherapy, thereby enhancing the efficacy of tumor treatment.…”

Section: Introductionmentioning

confidence: 99%

Ultrasonic Diagnosis and Treatment of Tumors Using Multifunctional Hollow Mesoporous Silicon Nanoparticles

Zhang,

Guo,

Liu

et al. 2024

ACS Appl. Nano Mater.

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In recent years, the application of hollow mesoporous silicon nanoparticles in the biomedical field has attracted much attention because of their excellent features. In this study, the sonosensitizer curcumin (Cur), the chemotherapy drug doxorubicin (Dox), and the perfluoropropane (C 3 F 8 ) gas were loaded into a multifunctional hollow mesoporous silica nanoparticle (MHMSN). The surface of MHMSN was modified with a biotin molecule and acid-sensitive groups (cis-aconitic anhydridepolyethylene glycol, CDM-PEG). The as-prepared multifunctional nanoparticle (CDF-MHMSN) demonstrates improved therapeutic efficacy and enhanced tumor contrast ultrasound performance. Surface-modified CDM-PEG can improve the blood circulation ability of nanoparticles and peel off in the acidic tumor microenvironment, which can enhance the endocytosis of cancer cells. As a sonosensitizer, Cur could generate reactive oxygen species (ROS) under ultrasound stimulation to kill tumor cells and reduce the multidrug resistance of tumor cells to the Dox by inhibiting the expression of P-glycoprotein. Overall, CDF-MHMSN exhibits good biocompatibility, excellent ultrasound imaging capability, and effective antitumor ability, which may contribute to improving the treatment strategy for hepatocellular carcinoma.

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“…Their smaller size on the range of 200 nm, could facilitate their entry into capillaries, increasing their numbers in smaller vessels. NBs were used for ultrasound contrast and molecular imaging 14,15 Cancer imaging 16,17 , sonoporation 18 , gene delivery 19,20 , Molecular imaging, noninvasive cancer therapy 21,22 , and BBBD [23][24][25][26][27] . Prior studies on NB-mediated BBBD primarily focused on establishing NBs for this purpose [23][24][25][26][27] .…”

Section: Introductionmentioning

confidence: 99%

Enhanced capillary delivery with nanobubble-mediated blood-brain barrier opening and advanced high resolution vascular segmentation

Gattegno,

Arbel,

Riess

et al. 2023

Preprint

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Overcoming the blood-brain barrier (BBB) is essential to enhance brain therapy. Here, we utilized nanoscale nanobubbles with focused ultrasound for targeted and improved BBB opening in mice. A microscopy method assessed BBB opening at a single blood vessel resolution employing a dual-dye labeling technique using green fluorescent molecules to label blood vessels and Evans blue brain-permeable dye for quantifying BBB extravasation. A UNET-based deep learning architecture enabled blood vessels segmentation, delivering comparable accuracy to manual segmentation with a significant time reduction. Segmentation outcomes were applied to the Evans blue channel to quantify extravasation of each blood vessel. Results were compared to microbubble-mediated BBB opening, where reduced extravasation was observed in capillaries with 2-6μm diameter. In comparison, nanobubbles yield an improved opening in these capillaries, and equivalent efficacy to that of microbubbles in larger vessels. These results indicate the potential of nanobubbles to serve as enhanced agents for BBB opening, amplifying bioeffects in capillaries while preserving comparable opening in larger vessels.

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Nanobubble-mediated cancer cell sonoporation using low-frequency ultrasound

Abstract: Ultrasound insonation of microbubbles can form transient pores in cell membranes that enable the delivery of non-permeable extracellular molecules to the cells. Reducing the size of microbubble contrast agents to...

Cited by 4 publications

References 67 publications

Intracranial Gene Delivery Mediated by Albumin-Based Nanobubbles and Low-Frequency Ultrasound

Intracranial Gene Delivery Mediated by Albumin-Based Nanobubbles and Low-Frequency Ultrasound

Ultrasonic Diagnosis and Treatment of Tumors Using Multifunctional Hollow Mesoporous Silicon Nanoparticles

Enhanced capillary delivery with nanobubble-mediated blood-brain barrier opening and advanced high resolution vascular segmentation

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