Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery

Deprez, Joke; Lajoinie, Guillaume; Engelen, Y.; Smedt, Stefaan C. De; Lentacker, Ine

doi:10.1016/j.addr.2021.02.015

Cited by 125 publications

(105 citation statements)

References 419 publications

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“…Microbubbles exposed to low-intensity US fields will oscillate (i.e., stable cavitation), while microbubbles exposed to higher intensities will collapse violently (i.e., inertial cavitation). Both types of cavitation lead to a number of bio-effects collectively known as sonopermeation, such as the formation of pores in cell membranes (sonoporation), enhanced endocytosis and increased vascular permeability, that improve the deposition of drugs in tumor tissue ( Snipstad et al, 2018 ; Deprez et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

et al. 2021

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Chemotherapy efficacy is often reduced by insufficient drug uptake in tumor cells. The combination of ultrasound and microbubbles (USMB) has been shown to improve drug delivery and to enhance the efficacy of several drugs in vitro and in vivo, through effects collectively known as sonopermeation. However, clinical translation of USMB therapy is hampered by the large variety of (non-clinical) US set-ups and US parameters that are used in these studies, which are not easily translated to clinical practice. In order to facilitate clinical translation, the aim of this study was to prove that USMB therapy using a clinical ultrasound system (Philips iU22) in combination with clinically approved microbubbles (SonoVue) leads to efficient in vitro sonopermeation. To this end, we measured the efficacy of USMB therapy for different US probes (S5-1, C5-1 and C9-4) and US parameters in FaDu cells. The US probe with the lowest central frequency (i.e. 1.6 MHz for S5-1) showed the highest USMB-induced intracellular uptake of the fluorescent dye SYTOX™ Green (SG). These SG uptake levels were comparable to or even higher than those obtained with a custom-built US system with optimized US parameters. Moreover, USMB therapy with both the clinical and the custom-built US system increased the cytotoxicity of the hydrophilic drug bleomycin. Our results demonstrate that a clinical US system can be used to perform USMB therapy as efficiently as a single-element transducer set-up with optimized US parameters. Therefore, future trials could be based on these clinical US systems, including validated US parameters, in order to accelerate successful translation of USMB therapy.

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Section: Introductionmentioning

confidence: 99%

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

et al. 2021

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“…The external stimuli, including the microwave, radiation, and ultrasound, are artificially imposed factors outside the body. The ultrasound as an external stimulus has significant advantages ( 26 , 30 ). CNC NPs realize the cascade release by combining the internal and external triggering stimuli.…”

Section: Discussionmentioning

confidence: 99%

“…In research of drug delivery, ultrasound has been reported that can help drugs permeate various physiological barriers. And some ultrasound phase change molecules make the method be a good source of external stimulus ( 30 ). The perfluorocarbon is a popular ultrasound triggering material, which occurs a phase change under the ultrasound, causing the carrier to rupture and release the loaded drug ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

Cascade Release Nanocarriers for the Triple-Negative Breast Cancer Near-Infrared Imaging and Photothermal-Chemo Synergistic Therapy

Zhou

et al. 2021

Front. Oncol.

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Triple-negative breast cancer (TNBC) has inadequate treatment approaches and a poor prognosis. It is urgent to develop new treatment approaches for TNBC. The combination of photothermal therapy (PTT) and chemotherapy is a very effective potential therapy for TNBC. However, asynchronous accumulation, unclear efficacy, and toxic side effects hinder the further promotion of this method. Therefore, we designed and constructed a new type of nanocarriers, the cascade release near-infrared imaging (NIFI) & thermal-chemo combination nanoparticles (CNC NPs), that can release drugs through the cascade of ultrasound triggering and pH responding to achieve the synchronous tumor accumulation, monitoring and synergistic treatment of two functional molecules. The key material of CNC NPs is the polydopamine (PDA), which, through self-assembling, forms a rigid shell that contains doxorubicin (DOX) and NIF fluorescent dye IR780 on the surface of the perfluorohexane (PFH) microbubbles. The results show that CNC NPs have a hollow core-shell structure with an average particle size of 97.3 ± 27.2 nm and have exceptional colloidal stability and photothermal conversion efficiency. The NPs can effectively perform cascade drug release through ultrasound triggering and pH responding. CNC NPs have good in vivo biological safety and excellent fluorescence imaging, drug delivery, and therapeutic abilities in the TNBC models. These results provide an experimental basis for the development of new clinical treatment methods for TNBC.

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“…Sonoporation and endocytosis can induce the uptake of molecules (fluorescent dextrans, calcein, propidium iodide, liposomes, plasmid DNA) that are otherwise not able to permeate intact cell membranes, because of their large size and/or low lipophilicity [24][25][26][27][28]. Similar to stable cavitation, sonoporation induced by inertial cavitation has been exploited to enhance the uptake of drugs and genes by cells [29][30][31][32]. Whether inertial cavitation can safely induce endocytosis still remains to be investigated.…”

Section: Mechanisms Underlying the Therapeutic Use Of Ultrasound And Microbubblesmentioning

confidence: 99%

Ultrasound and Microbubbles for the Treatment of Ocular Diseases: From Preclinical Research towards Clinical Application

et al. 2021

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The unique anatomy of the eye and the presence of various biological barriers make efficacious ocular drug delivery challenging, particularly in the treatment of posterior eye diseases. This review focuses on the combination of ultrasound and microbubbles (USMB) as a minimally invasive method to improve the efficacy and targeting of ocular drug delivery. An extensive overview is given of the in vitro and in vivo studies investigating the mechanical effects of ultrasound-driven microbubbles aiming to: (i) temporarily disrupt the blood–retina barrier in order to enhance the delivery of systemically administered drugs into the eye, (ii) induce intracellular uptake of anticancer drugs and macromolecules and (iii) achieve targeted delivery of genes, for the treatment of ocular malignancies and degenerative diseases. Finally, the safety and tolerability aspects of USMB, essential for the translation of USMB to the clinic, are discussed.

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Opening doors with ultrasound and microbubbles: Beating biological barriers to promote drug delivery

Cited by 125 publications

References 419 publications

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

Ultrasound-Mediated Drug Delivery With a Clinical Ultrasound System: In Vitro Evaluation

Cascade Release Nanocarriers for the Triple-Negative Breast Cancer Near-Infrared Imaging and Photothermal-Chemo Synergistic Therapy

Ultrasound and Microbubbles for the Treatment of Ocular Diseases: From Preclinical Research towards Clinical Application

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