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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

Cell viability measurements.(a) Cell viability was determined after contrast-agent-treated cells were exposed to the indicated energy modalities. Statistically significant differences between two independent groups were determined using the statistical methods described in the Methods. Data are mean and SD values. *p < 0.05; **p < 0.01; ***p < 0.001. (b) Final temperatures measured after contrast-agent-treated cells were exposed the indicated energy modalities. Temperature data are mean and SD values.
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f5: Cell viability measurements.(a) Cell viability was determined after contrast-agent-treated cells were exposed to the indicated energy modalities. Statistically significant differences between two independent groups were determined using the statistical methods described in the Methods. Data are mean and SD values. *p < 0.05; **p < 0.01; ***p < 0.001. (b) Final temperatures measured after contrast-agent-treated cells were exposed the indicated energy modalities. Temperature data are mean and SD values.

Mentions: Since we demonstrated that exposing AuNDs to ultrasound combined with laser radiation can improve the rate of AuNRs release, we next hypothesized that carrying and releasing more AuNRs to the target tumor site will enhance the photothermal therapeutic efficiency. To test this hypothesis, in vitro cell viability was measured after BNL 1ME A.7R.1 mouse liver cancer cells were incubated with AuNDs and AuMBs followed by the application of three energy modalities, and the thermal effects were examined by using a thermocouple. Cell viability was reduced to 75% or 80% after AuMBs- or AuNDs-treated cells were exposed to ultrasound (Fig. 5a), and the temperatures measured after the treatment were 20.87 °C or 20.93 °C, respectively (Fig. 5b). It suggests that the reduced cell viability is due to ultrasound-induced cavitation. Cell viability was reduced to 75% after AuMBs- or AuNDs-treated cells were exposed to laser radiation (Fig. 5a), and the temperatures measured after the treatment were 40.6 °C or 50.87 °C, respectively (Fig. 5b). It suggests that the reduced cell viability is due to the laser radiation-induced thermal effect. The viability of AuNDs-treated cells was significantly lower when cells were exposed to ultrasound and laser radiation simultaneously compared to either energy modality alone (Fig. 5a). Although the same result was obtained for AuMBs-treated tumor cells, it was clear that it was significantly more feasible to reduce the cell viability of AuNDs-treated tumor cells by exposing them to ultrasound and laser radiation simultaneously. Notably, after cells were exposed to ultrasound and laser radiation simultaneously, the viability of AuNDs-treated cells was significantly reduced from 85% or 50% to 20% in comparison with control cells (no contrast agents treatment) or AuMBs-treated cells. As shown in Fig. 5b, the temperature measured after AuNDs-treated cells were exposed to ultrasound and laser radiation simultaneously was increased to 61.33 °C that was obviously higher than other groups. This represents conclusive evidence that tumor cells are effectively killed by treatment with AuNDs followed by exposure to ultrasound and laser radiation simultaneously in vitro, and it suggests that ultrasound-induced cavitation and the laser radiation-induced thermal effect exert the synergistic effect on reducing the cell viability of AuNDs-treated cells.


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)

Cell viability measurements.(a) Cell viability was determined after contrast-agent-treated cells were exposed to the indicated energy modalities. Statistically significant differences between two independent groups were determined using the statistical methods described in the Methods. Data are mean and SD values. *p < 0.05; **p < 0.01; ***p < 0.001. (b) Final temperatures measured after contrast-agent-treated cells were exposed the indicated energy modalities. Temperature data are mean and SD values.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Cell viability measurements.(a) Cell viability was determined after contrast-agent-treated cells were exposed to the indicated energy modalities. Statistically significant differences between two independent groups were determined using the statistical methods described in the Methods. Data are mean and SD values. *p < 0.05; **p < 0.01; ***p < 0.001. (b) Final temperatures measured after contrast-agent-treated cells were exposed the indicated energy modalities. Temperature data are mean and SD values.
Mentions: Since we demonstrated that exposing AuNDs to ultrasound combined with laser radiation can improve the rate of AuNRs release, we next hypothesized that carrying and releasing more AuNRs to the target tumor site will enhance the photothermal therapeutic efficiency. To test this hypothesis, in vitro cell viability was measured after BNL 1ME A.7R.1 mouse liver cancer cells were incubated with AuNDs and AuMBs followed by the application of three energy modalities, and the thermal effects were examined by using a thermocouple. Cell viability was reduced to 75% or 80% after AuMBs- or AuNDs-treated cells were exposed to ultrasound (Fig. 5a), and the temperatures measured after the treatment were 20.87 °C or 20.93 °C, respectively (Fig. 5b). It suggests that the reduced cell viability is due to ultrasound-induced cavitation. Cell viability was reduced to 75% after AuMBs- or AuNDs-treated cells were exposed to laser radiation (Fig. 5a), and the temperatures measured after the treatment were 40.6 °C or 50.87 °C, respectively (Fig. 5b). It suggests that the reduced cell viability is due to the laser radiation-induced thermal effect. The viability of AuNDs-treated cells was significantly lower when cells were exposed to ultrasound and laser radiation simultaneously compared to either energy modality alone (Fig. 5a). Although the same result was obtained for AuMBs-treated tumor cells, it was clear that it was significantly more feasible to reduce the cell viability of AuNDs-treated tumor cells by exposing them to ultrasound and laser radiation simultaneously. Notably, after cells were exposed to ultrasound and laser radiation simultaneously, the viability of AuNDs-treated cells was significantly reduced from 85% or 50% to 20% in comparison with control cells (no contrast agents treatment) or AuMBs-treated cells. As shown in Fig. 5b, the temperature measured after AuNDs-treated cells were exposed to ultrasound and laser radiation simultaneously was increased to 61.33 °C that was obviously higher than other groups. This represents conclusive evidence that tumor cells are effectively killed by treatment with AuNDs followed by exposure to ultrasound and laser radiation simultaneously in vitro, and it suggests that ultrasound-induced cavitation and the laser radiation-induced thermal effect exert the synergistic effect on reducing the cell viability of AuNDs-treated cells.

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