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Nanodroplet-Vaporization-Assisted Sonoporation for Highly Effective Delivery of Photothermal Treatment.

Liu WW, Liu SW, Liou YR, Wu YH, Yang YC, Wang CR, Li PC - Sci Rep (2016)

Bottom Line: This study used nanodroplets to significantly enhance the effectiveness of sonoporation relative to 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.

View Article: PubMed Central - PubMed

Affiliation: National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei 106, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

AuNDs-assisted PPTT.Schematic of the concept and mechanism of AuNDs-assisted PPTT for a tumor. A detailed description is presented in the last paragraph of the Results. Briefly, in the first step, after AuNDs are loaded into the tumor, the EPR effect of the AuNDs in the tumor is increased due to their smallness. In the second step, optically triggered optical droplet vaporization causes expansion of AuNDs and also instability of their HSA shell. In the third step, acoustic cavitation is induced and causes the violent collapse of the vaporized AuNDs, and the subsequent more-permeable defects allow more AuNDs to be delivered to the tumor tissue. In the fourth step, the enhanced EPR effect of AuNDs promotes more AuNRs to be expelled from AuNDs and subsequently delivered to the tumor, thereby improving the thermal ablation efficiency of PPTT.
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f10: AuNDs-assisted PPTT.Schematic of the concept and mechanism of AuNDs-assisted PPTT for a tumor. A detailed description is presented in the last paragraph of the Results. Briefly, in the first step, after AuNDs are loaded into the tumor, the EPR effect of the AuNDs in the tumor is increased due to their smallness. In the second step, optically triggered optical droplet vaporization causes expansion of AuNDs and also instability of their HSA shell. In the third step, acoustic cavitation is induced and causes the violent collapse of the vaporized AuNDs, and the subsequent more-permeable defects allow more AuNDs to be delivered to the tumor tissue. In the fourth step, the enhanced EPR effect of AuNDs promotes more AuNRs to be expelled from AuNDs and subsequently delivered to the tumor, thereby improving the thermal ablation efficiency of PPTT.

Mentions: The potential mechanism is illustrated schematically in Fig. 10. In the first step, when AuNDs are loaded into a tumor and flow into a leaky vessel located inside the tumor, the nanosized AuNDs can easily pass through the endothelial gaps (with a range between 0.2 to 1.2 μm in mouse tumors) to improve the EPR effect of AuNDs. Since the AuNDs are relative stable carriers, this enhances the delivery of AuNRs to tumor tissue. In the second step, laser-induced optical droplet vaporization is induced to expand the AuNDs to several microns in diameter due to the absorbance of the optical energy by the encapsulated AuNRs. Meanwhile, the surface of the HSA shell of the expanded AuNDs becomes unstable due to the cracks, resulting in leakage of the AuNRs and facilitating the activation of the subsequent acoustic cavitation. In the third step, AuNDs were fully vaporized to AuMBs. Since the membrane of the HSA shell becomes even more unstable, acoustic cavitation is easy to trigger to induce the collapse of AuMBs. AuNRs are subsequently released from the violently collapsed AuMBs to expand the PPTT-affected area. The shock wave generated by the violently collapsed AuMBs also induces more-permeable defects in the endothelial walls that allow more AuNDs to pass through during the next cycle of energy application. In the final step, by continuously applying the AuNDs-assisted PPTT for a while, tumor tissue is thermal ablated by optically induced hyperthermia via heating of the AuNRs released from AuNDs. AuNRs play a self-activating role in this process by not only enhancing the vaporization in the first three steps but also for inducing thermal ablation in the last step.


Nanodroplet-Vaporization-Assisted Sonoporation for Highly Effective Delivery of Photothermal Treatment.

Liu WW, Liu SW, Liou YR, Wu YH, Yang YC, Wang CR, Li PC - Sci Rep (2016)

AuNDs-assisted PPTT.Schematic of the concept and mechanism of AuNDs-assisted PPTT for a tumor. A detailed description is presented in the last paragraph of the Results. Briefly, in the first step, after AuNDs are loaded into the tumor, the EPR effect of the AuNDs in the tumor is increased due to their smallness. In the second step, optically triggered optical droplet vaporization causes expansion of AuNDs and also instability of their HSA shell. In the third step, acoustic cavitation is induced and causes the violent collapse of the vaporized AuNDs, and the subsequent more-permeable defects allow more AuNDs to be delivered to the tumor tissue. In the fourth step, the enhanced EPR effect of AuNDs promotes more AuNRs to be expelled from AuNDs and subsequently delivered to the tumor, thereby improving the thermal ablation efficiency of PPTT.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837361&req=5

f10: AuNDs-assisted PPTT.Schematic of the concept and mechanism of AuNDs-assisted PPTT for a tumor. A detailed description is presented in the last paragraph of the Results. Briefly, in the first step, after AuNDs are loaded into the tumor, the EPR effect of the AuNDs in the tumor is increased due to their smallness. In the second step, optically triggered optical droplet vaporization causes expansion of AuNDs and also instability of their HSA shell. In the third step, acoustic cavitation is induced and causes the violent collapse of the vaporized AuNDs, and the subsequent more-permeable defects allow more AuNDs to be delivered to the tumor tissue. In the fourth step, the enhanced EPR effect of AuNDs promotes more AuNRs to be expelled from AuNDs and subsequently delivered to the tumor, thereby improving the thermal ablation efficiency of PPTT.
Mentions: The potential mechanism is illustrated schematically in Fig. 10. In the first step, when AuNDs are loaded into a tumor and flow into a leaky vessel located inside the tumor, the nanosized AuNDs can easily pass through the endothelial gaps (with a range between 0.2 to 1.2 μm in mouse tumors) to improve the EPR effect of AuNDs. Since the AuNDs are relative stable carriers, this enhances the delivery of AuNRs to tumor tissue. In the second step, laser-induced optical droplet vaporization is induced to expand the AuNDs to several microns in diameter due to the absorbance of the optical energy by the encapsulated AuNRs. Meanwhile, the surface of the HSA shell of the expanded AuNDs becomes unstable due to the cracks, resulting in leakage of the AuNRs and facilitating the activation of the subsequent acoustic cavitation. In the third step, AuNDs were fully vaporized to AuMBs. Since the membrane of the HSA shell becomes even more unstable, acoustic cavitation is easy to trigger to induce the collapse of AuMBs. AuNRs are subsequently released from the violently collapsed AuMBs to expand the PPTT-affected area. The shock wave generated by the violently collapsed AuMBs also induces more-permeable defects in the endothelial walls that allow more AuNDs to pass through during the next cycle of energy application. In the final step, by continuously applying the AuNDs-assisted PPTT for a while, tumor tissue is thermal ablated by optically induced hyperthermia via heating of the AuNRs released from AuNDs. AuNRs play a self-activating role in this process by not only enhancing the vaporization in the first three steps but also for inducing thermal ablation in the last step.

Bottom Line: This study used nanodroplets to significantly enhance the effectiveness of sonoporation relative to 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.

View Article: PubMed Central - PubMed

Affiliation: National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei 106, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus