Abstract
Techniques that increase the permeability of the cell membrane and transfer drugs or genes to cells have been actively developed as effective therapeutic modalities. Also, in line with the development of these drug delivery techniques, the establishment of tools to verify the techniques at the cellular level is strongly required. In this study, we demonstrated an optical imaging platform integrated with an ultrasound application system to verify the feasibility of safe and efficient drug delivery through the cell membrane using ultrasound-microbubble cavitation. To examine the potential of the platform, fluorescence images of both Fura-2 AM and propidium iodide (PI) to measure calcium flux changes and intracellular PI delivery, respectively, during and after the ultrasound-microbubble cavitation in the cervical cancer cell were acquired. Using the optical imaging platform, we determined that calcium flux increased immediately after the ultrasound-microbubble cavitation and were restored to normal levels, and fluorescence signals from intracellular PI increased gradually after the cavitation. The results acquired by the platform indicated that ultrasound-microbubble cavitation can deliver PI into the cervical cancer cell without irreversible damage of the cell membrane. The application of an additional fluorescent imaging module and high-speed imaging modalities can provide further improvement of the performance of this platform. Also, as additional studies in ultrasound instrumentations to measure real-time cavitation signals progress, we believe that the ultrasound-microbubble cavitation-based sonoporation can be employed for safe and efficient drug and gene delivery to various cancer cells.
Highlights
Drug delivery is a series of modalities of various physical and chemical techniques to deliver, release, and control a specific drug, so that it has an optimal effect even with a small dose [1]
In images of calcium flux changes over time based on ultrasound irradiation, the ultrasound-induced microbubble cavitation offered a significant increase in the intracellular calcium concentration in the cervical cancer cell
Using the optical imaging platform integrated with the ultrasound application system, we derived the ultrasoundbased cavitation of a microbubble attached to a membrane of a cervical cancer cell, and obtained longitudinal fluorescence images of calcium flux and intracellular propidium iodide (PI) uptake to explore the feasibility of effective and noninvasive drug or gene delivery in cervical cancer by microbubble-mediated sonoporation
Summary
Drug delivery is a series of modalities of various physical and chemical techniques to deliver, release, and control a specific drug, so that it has an optimal effect even with a small dose [1]. Drug delivery techniques that can efficiently deliver existing drugs are economically effective because developing more efficient drugs involves a lot of costs. In addition to methods of using the transporters, studies that transfer energies such as electrical potentials [7,8] or nanoparticle-mediated light [9,10,11] to deliver drugs to cancer cells have been conducted. Among these drug delivery techniques, ultrasound-based drug delivery has advantages of being highly biopermeable, having high accuracy, and not permanently damaging other cells or tissues. The fundamental of drug delivery by the ultrasoundmicrobubble cavitation is that drugs or chemical compounds, which do not generally enter the cell, can penetrate the cell due to increased permeability by the cavitation
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