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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

TEM for cellular investigation.(a) Cells in a tumor that was not treated. (b) Magnified image of the area indicated by the rectangle in (a). (c–e) AuNDs located in tumors treated with PPTT for only 30 seconds. Black arrows in (c): disrupted sites of cellular membrane. White stars in (c): intact AuNDs. (f) After AuNDs-assisted PPTT is performed for 5 minutes, no droplets or bubbles were found, and the cellular structures no longer appeared integrated. (g) Magnified image of the area indicated by the rectangle in (f). Many free AuNRs are evident throughout the fractured cells.
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f9: TEM for cellular investigation.(a) Cells in a tumor that was not treated. (b) Magnified image of the area indicated by the rectangle in (a). (c–e) AuNDs located in tumors treated with PPTT for only 30 seconds. Black arrows in (c): disrupted sites of cellular membrane. White stars in (c): intact AuNDs. (f) After AuNDs-assisted PPTT is performed for 5 minutes, no droplets or bubbles were found, and the cellular structures no longer appeared integrated. (g) Magnified image of the area indicated by the rectangle in (f). Many free AuNRs are evident throughout the fractured cells.

Mentions: TEM was used to evaluate the changes in AuNDs and cellular damage resulting from AuNDs-assisted PPTT in treated tumors. As shown in Fig. 9a, untreated tumors appeared with integrated cellular structures; the magnified organelle shown in Fig. 9b was an integrated mitochondrion located within the square in Fig. 9a. After AuNDs located in tumor were exposed to PPTT for 30 seconds, it was enlarged to several microns in diameter—as expected due to the vaporization—with several cracks appearing on the outer membrane of the droplets, in contrast to AuNDs (labeled by white stars) that had not been expanded to disrupt the membrane integrity (Fig. 9c). Furthermore, sonoporation-induced cellular plasma membrane disruption was observed and pointed out by black arrows in Fig. 9c. Consistent with a previously reported concept28, AuNRs were subsequently pushed to the membrane of AuNDs or expelled from AuNDs during vaporization (Fig. 9d). In some nanosized droplets, AuNRs were still encapsulated into the HSA shell due to the received energy being insufficient for vaporization to push the AuNRs out from AuNDs (Fig. 9e). After PPTT was applied for 5 minutes, most of the AuNDs had been destroyed and the cellular structure was disrupted (Fig. 9f), with damaged organelles evident under higher magnification and the AuNRs being dispersed throughout the tumor tissue (Fig. 9g). These results provide direct evidence of changes in AuNDs during PPTT in vivo and damage at the cellular level, and they help us to characterize the in vivo loaded AuNDs and understand the potential mechanism of AuNDs-assisted PPTT in vivo.


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)

TEM for cellular investigation.(a) Cells in a tumor that was not treated. (b) Magnified image of the area indicated by the rectangle in (a). (c–e) AuNDs located in tumors treated with PPTT for only 30 seconds. Black arrows in (c): disrupted sites of cellular membrane. White stars in (c): intact AuNDs. (f) After AuNDs-assisted PPTT is performed for 5 minutes, no droplets or bubbles were found, and the cellular structures no longer appeared integrated. (g) Magnified image of the area indicated by the rectangle in (f). Many free AuNRs are evident throughout the fractured cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f9: TEM for cellular investigation.(a) Cells in a tumor that was not treated. (b) Magnified image of the area indicated by the rectangle in (a). (c–e) AuNDs located in tumors treated with PPTT for only 30 seconds. Black arrows in (c): disrupted sites of cellular membrane. White stars in (c): intact AuNDs. (f) After AuNDs-assisted PPTT is performed for 5 minutes, no droplets or bubbles were found, and the cellular structures no longer appeared integrated. (g) Magnified image of the area indicated by the rectangle in (f). Many free AuNRs are evident throughout the fractured cells.
Mentions: TEM was used to evaluate the changes in AuNDs and cellular damage resulting from AuNDs-assisted PPTT in treated tumors. As shown in Fig. 9a, untreated tumors appeared with integrated cellular structures; the magnified organelle shown in Fig. 9b was an integrated mitochondrion located within the square in Fig. 9a. After AuNDs located in tumor were exposed to PPTT for 30 seconds, it was enlarged to several microns in diameter—as expected due to the vaporization—with several cracks appearing on the outer membrane of the droplets, in contrast to AuNDs (labeled by white stars) that had not been expanded to disrupt the membrane integrity (Fig. 9c). Furthermore, sonoporation-induced cellular plasma membrane disruption was observed and pointed out by black arrows in Fig. 9c. Consistent with a previously reported concept28, AuNRs were subsequently pushed to the membrane of AuNDs or expelled from AuNDs during vaporization (Fig. 9d). In some nanosized droplets, AuNRs were still encapsulated into the HSA shell due to the received energy being insufficient for vaporization to push the AuNRs out from AuNDs (Fig. 9e). After PPTT was applied for 5 minutes, most of the AuNDs had been destroyed and the cellular structure was disrupted (Fig. 9f), with damaged organelles evident under higher magnification and the AuNRs being dispersed throughout the tumor tissue (Fig. 9g). These results provide direct evidence of changes in AuNDs during PPTT in vivo and damage at the cellular level, and they help us to characterize the in vivo loaded AuNDs and understand the potential mechanism of AuNDs-assisted PPTT in vivo.

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