Abstract
Sonoporation refers to the use of ultrasound and acoustic cavitation to temporarily enhance the permeability of cellular membranes so as to enhance the delivery efficiency of therapeutic agents into cells. Microbubble-based ultrasound contrast agents are often used to facilitate these cavitation effects. This study used nanodroplets to significantly enhance the effectiveness of sonoporation relative to using conventional microbubbles. Significant enhancements were demonstrated both in vitro and in vivo by using gold nanorods encapsulated in nanodroplets for implementing plasmonic photothermal therapy. Combined excitation by ultrasound and laser radiation is used to trigger the gold nanodroplets to induce a liquid-to-gas phase change, which induces cavitation effects that are three-to-fivefold stronger than when using conventional microbubbles. Enhanced cavitation also leads to significant enhancement of the sonoporation effects. Our in vivo results show that nanodroplet-vaporization-assisted sonoporation can increase the treatment temperature by more than 10 °C above that achieved by microbubble-based sonoporation.
Highlights
The enhancement efficacy of ultrasound-directed drug delivery has been greatly influenced by advances in contrast agents[11]
To check whether the optical properties of the AuNRs were tuned, the size distribution of AuNRs was determining under transmission electron microscopy (TEM) and the optical density (OD) of the AuNRs was investigated using spectrophotometry
Cryogenic TEM was used to investigate the spherical structure of the AuNDs to ensure that the AuNRs had been successful encapsulated within the synthesized AuNDs
Summary
The enhancement efficacy of ultrasound-directed drug delivery has been greatly influenced by advances in contrast agents[11]. The most popular type of contrast agent is MBs, which have been developed over many years and are usually applied to facilitate sonoporation in drug delivery and to enhance ultrasound imaging contrast. We successfully applied dual-modality targeting MBs comprising encapsulated AuNRs with an albumin shell and gas-filled core for enhancing the efficiency of AuNRs delivery through active targeting and sonoporation[15]. That work demonstrated the ability to enhance the therapeutic efficiency, due to the limitations of gas-filled MBs we proposed replacing them with NDs in order to increase the vehicle stability and exert stronger cavitation effects to achieve enhanced extravasation for the delivery of AuNRs. The present study developed NDs composed of a low-boiling-point dodecafluorocarbon (DDFC) liquid core and a human serum albumin (HSA) protein shell. The synergy among various mechanisms by which sonoporation facilitates the AuNDs-assisted PPTT was investigated
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