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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

Enhanced cavitation effect and efficiency of AuNRs release.(a) Differential ICD–time curve showing the change in the cavitation effect induced by the indicated contrast-agent-assisted energy application methods. Upon exposure to ultrasound and laser radiation simultaneously for 5 minutes, the dICD value was enhanced by 3.3 fold for AuNDs compared to AuMBs with the same treatment, and it was enhanced by 3.4 fold compared to AuNDs exposed to ultrasound only. The time zero (t = 0) labeled at the X axis is the starting time to transmit the ultrasound signal from the 1 MHz transmitting transducer, and the amount of cavitation signals are collected by the 10 MHz receiving transducer with a 13-seconds delayed. (b,c) The destruction ratio and the rate of AuNRs release were measured after AuNDs or AuMBs were exposed to the indicated energy modalities. The initial OD values of the same number of the intact AuNDs or AuMBs before exposed to the indicated energy modalities were 0.084 ± 0.006 or 0.068 ± 0.009 (mean ± SD), respectively. 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. (d) The plot showing the OD values function to the different concentrations of free AuNRs. Temperatures labeled near the black circles indicate the final temperatures after indicated concentration of free AuNRs was exposed to laser radiation for 5 minutes. The initial temperature before the treatment is 18.2 °C. The R-squared is 0.99211 and the equation for the best fit regression line is y = 0.2089x-0.002.
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f4: Enhanced cavitation effect and efficiency of AuNRs release.(a) Differential ICD–time curve showing the change in the cavitation effect induced by the indicated contrast-agent-assisted energy application methods. Upon exposure to ultrasound and laser radiation simultaneously for 5 minutes, the dICD value was enhanced by 3.3 fold for AuNDs compared to AuMBs with the same treatment, and it was enhanced by 3.4 fold compared to AuNDs exposed to ultrasound only. The time zero (t = 0) labeled at the X axis is the starting time to transmit the ultrasound signal from the 1 MHz transmitting transducer, and the amount of cavitation signals are collected by the 10 MHz receiving transducer with a 13-seconds delayed. (b,c) The destruction ratio and the rate of AuNRs release were measured after AuNDs or AuMBs were exposed to the indicated energy modalities. The initial OD values of the same number of the intact AuNDs or AuMBs before exposed to the indicated energy modalities were 0.084 ± 0.006 or 0.068 ± 0.009 (mean ± SD), respectively. 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. (d) The plot showing the OD values function to the different concentrations of free AuNRs. Temperatures labeled near the black circles indicate the final temperatures after indicated concentration of free AuNRs was exposed to laser radiation for 5 minutes. The initial temperature before the treatment is 18.2 °C. The R-squared is 0.99211 and the equation for the best fit regression line is y = 0.2089x-0.002.

Mentions: Inertial cavitation is a physical phenomenon in which vapor bubbles collapse violently at sufficient acoustic pressures. To confirm that inertial cavitation was generated when optically vaporized AuNDs were exposed to ultrasound, the cavitation signals were measured according to a previously described method39, the system setup for which is illustrated in Fig. 3. Briefly, we measured broadband signals from the system, and the inertial cavitation dose (ICD) value was calculated as the root-mean-square (RMS) value of the spectrum between 9.5 MHz and 10.5 MHz. The differential ICD (dICD) value was obtained by subtracting the RMS amplitude of the contrast agent from that of water. The results showed that the dICD value increased gradually when AuNDs were exposed to ultrasound and laser radiation simultaneously (Fig. 4a). In contrast, the dICD value decreased gradually during the 5-minute exposure to ultrasound, while the value was difficult to calculate when AuNDs were exposed only to laser radiation. We also exposed AuMBs to ultrasound and laser radiation simultaneously, and found that the dICD value was also gradually reduced during the 5-minute exposure. A stronger and gradually increasing cavitation effect was found for AuNDs relative to AuMBs under exposure to ultrasound and laser radiation simultaneously. These data together indicate that the enhanced cavitation effect is triggered when AuNDs are exposed to ultrasound and laser radiation simultaneously, and it also suggests that the cavitation is predominantly induced by the ultrasound rather than the laser radiation.


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)

Enhanced cavitation effect and efficiency of AuNRs release.(a) Differential ICD–time curve showing the change in the cavitation effect induced by the indicated contrast-agent-assisted energy application methods. Upon exposure to ultrasound and laser radiation simultaneously for 5 minutes, the dICD value was enhanced by 3.3 fold for AuNDs compared to AuMBs with the same treatment, and it was enhanced by 3.4 fold compared to AuNDs exposed to ultrasound only. The time zero (t = 0) labeled at the X axis is the starting time to transmit the ultrasound signal from the 1 MHz transmitting transducer, and the amount of cavitation signals are collected by the 10 MHz receiving transducer with a 13-seconds delayed. (b,c) The destruction ratio and the rate of AuNRs release were measured after AuNDs or AuMBs were exposed to the indicated energy modalities. The initial OD values of the same number of the intact AuNDs or AuMBs before exposed to the indicated energy modalities were 0.084 ± 0.006 or 0.068 ± 0.009 (mean ± SD), respectively. 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. (d) The plot showing the OD values function to the different concentrations of free AuNRs. Temperatures labeled near the black circles indicate the final temperatures after indicated concentration of free AuNRs was exposed to laser radiation for 5 minutes. The initial temperature before the treatment is 18.2 °C. The R-squared is 0.99211 and the equation for the best fit regression line is y = 0.2089x-0.002.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Enhanced cavitation effect and efficiency of AuNRs release.(a) Differential ICD–time curve showing the change in the cavitation effect induced by the indicated contrast-agent-assisted energy application methods. Upon exposure to ultrasound and laser radiation simultaneously for 5 minutes, the dICD value was enhanced by 3.3 fold for AuNDs compared to AuMBs with the same treatment, and it was enhanced by 3.4 fold compared to AuNDs exposed to ultrasound only. The time zero (t = 0) labeled at the X axis is the starting time to transmit the ultrasound signal from the 1 MHz transmitting transducer, and the amount of cavitation signals are collected by the 10 MHz receiving transducer with a 13-seconds delayed. (b,c) The destruction ratio and the rate of AuNRs release were measured after AuNDs or AuMBs were exposed to the indicated energy modalities. The initial OD values of the same number of the intact AuNDs or AuMBs before exposed to the indicated energy modalities were 0.084 ± 0.006 or 0.068 ± 0.009 (mean ± SD), respectively. 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. (d) The plot showing the OD values function to the different concentrations of free AuNRs. Temperatures labeled near the black circles indicate the final temperatures after indicated concentration of free AuNRs was exposed to laser radiation for 5 minutes. The initial temperature before the treatment is 18.2 °C. The R-squared is 0.99211 and the equation for the best fit regression line is y = 0.2089x-0.002.
Mentions: Inertial cavitation is a physical phenomenon in which vapor bubbles collapse violently at sufficient acoustic pressures. To confirm that inertial cavitation was generated when optically vaporized AuNDs were exposed to ultrasound, the cavitation signals were measured according to a previously described method39, the system setup for which is illustrated in Fig. 3. Briefly, we measured broadband signals from the system, and the inertial cavitation dose (ICD) value was calculated as the root-mean-square (RMS) value of the spectrum between 9.5 MHz and 10.5 MHz. The differential ICD (dICD) value was obtained by subtracting the RMS amplitude of the contrast agent from that of water. The results showed that the dICD value increased gradually when AuNDs were exposed to ultrasound and laser radiation simultaneously (Fig. 4a). In contrast, the dICD value decreased gradually during the 5-minute exposure to ultrasound, while the value was difficult to calculate when AuNDs were exposed only to laser radiation. We also exposed AuMBs to ultrasound and laser radiation simultaneously, and found that the dICD value was also gradually reduced during the 5-minute exposure. A stronger and gradually increasing cavitation effect was found for AuNDs relative to AuMBs under exposure to ultrasound and laser radiation simultaneously. These data together indicate that the enhanced cavitation effect is triggered when AuNDs are exposed to ultrasound and laser radiation simultaneously, and it also suggests that the cavitation is predominantly induced by the ultrasound rather than the laser radiation.

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