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Ultrasound-mediated local drug and gene delivery using nanocarriers.

Zhou QL, Chen ZY, Wang YX, Yang F, Lin Y, Liao YY - Biomed Res Int (2014)

Bottom Line: These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy.The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle.In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound Medicine, Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.

ABSTRACT
With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

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PDI images of New Zealand rabbit kidney. (a) The image was black before the intravenous injection of nanobubbles in rabbit. (b) After intravenous injection of the nanobubbles, PDI enhancement was observed. (c) In vitro contrast enhanced US imaging showed the gray-scale intensities of siRNA-NBs decreased more slowly than the gas-cored liposomes [47, 48].
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fig2: PDI images of New Zealand rabbit kidney. (a) The image was black before the intravenous injection of nanobubbles in rabbit. (b) After intravenous injection of the nanobubbles, PDI enhancement was observed. (c) In vitro contrast enhanced US imaging showed the gray-scale intensities of siRNA-NBs decreased more slowly than the gas-cored liposomes [47, 48].

Mentions: The nanoscaled ultrasound contrast agent (UCA) can also be used as a theranostic agent with good imaging ability. PLGA nanobubbles show good stability, high-efficiency coating, stable loading, small size, and controlled and efficiency release. Wheatley et al. [49] developed a surfactant-stabilized UCA by differential centrifugation method at a speed of 300 rpm for 3 min. The UCA had an average diameter of 450 nm, which gave 25.5 dB enhancements in vitro at a dose of 10 microL/mL (with a half-life of 13 min). Moreover, the UCA produced wonderful in vivo power Doppler images and grey-scale pulse inversion harmonic images at low sound power levels. Xing et al. [47] fabricated a new kind of biocompatible nanobubbles by ultrasonication of a mixture of polyoxyethylene 40 stearate (PEG 40S) and Span 60 followed by differential centrifugation method. The nanobubbles had a precisely controlled mean size which was small enough to permeate through tumor cell membrane. The differential centrifugation method was an effective method for size separation of particles. It produced narrow size distributions for certain applications. Under the protection of perfluoropropane gas, the bubbles remained stable for more than two weeks. The acoustic behavior of the nanosized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. The figure showed an example of the reflectivity enhancement by comparing two images, at the beginning of the injection and at the maximum enhancement after injection, respectively. The image appeared black due to no nanobubbles (Figure 2(a)); however, when the nanobubbles were injected in rabbit, marked and complete power Doppler enhancement appeared immediately following slow infusion of the contrast agent and color flare appeared in the renal parenchyma (Figure 2(b)). In vivo power Doppler imaging (PDI) enhancement was observed for about 1 min, suggesting such nanobubbles were stable enough for ultrasound imaging. At the condition of 20 g sample (for 5 min), the maximum enhancement was not observed in PDI modes. This was most likely because of differences in the concentration and stability of the nanobubbles. The imaging observation along with the precipitations for 5 min samples assuredly pointed to better stability for the 3 min samples. According to the experiments, the 3 min and 20 g sample seemed to be the most promising choice for tumor imaging and US-mediated targeted therapy. Yin et al. [48] developed the US-sensitive siRNA-nanobubbles (NBs, referred to as gas-cored liposomes) for tumor imaging and targeted drug delivery. Effective accumulation of the nanobubbles in tumor tissues could be achieved via the EPR effect. The changes of gray-scale intensities before and after US exposure showed that the siRNA-NBs had good US sensitivity, which hold great potential for US-mediated in vivo therapy for tumors. According to the further results, the gray-scale intensities of siRNA-NBs decreased more slowly than the gas-cored liposomes (Figure 2(c)), suggesting good stability; moreover, low-frequency US triggered similarly prompt decrease in gray-scale intensity for both the siRNA-NBs and the liposomes, suggesting that siRNA micelle adhering to liposome surfaces did not alter the sensitivity of the liposomes to ultrasound. With the aid of low-frequency US exposure, siRNA micelles were released from the siRNA-NBs and delivered into tumor cells. Wang et al. [3] used coumarin as a model drug loaded into nanobubbles to investigate the drug delivery potential to cells. The results showed that the nanobubbles (composed of 1% of Tween 80, 3 mg/mL of lipid) presented best in vivo imaging of liver.


Ultrasound-mediated local drug and gene delivery using nanocarriers.

Zhou QL, Chen ZY, Wang YX, Yang F, Lin Y, Liao YY - Biomed Res Int (2014)

PDI images of New Zealand rabbit kidney. (a) The image was black before the intravenous injection of nanobubbles in rabbit. (b) After intravenous injection of the nanobubbles, PDI enhancement was observed. (c) In vitro contrast enhanced US imaging showed the gray-scale intensities of siRNA-NBs decreased more slowly than the gas-cored liposomes [47, 48].
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4150504&req=5

fig2: PDI images of New Zealand rabbit kidney. (a) The image was black before the intravenous injection of nanobubbles in rabbit. (b) After intravenous injection of the nanobubbles, PDI enhancement was observed. (c) In vitro contrast enhanced US imaging showed the gray-scale intensities of siRNA-NBs decreased more slowly than the gas-cored liposomes [47, 48].
Mentions: The nanoscaled ultrasound contrast agent (UCA) can also be used as a theranostic agent with good imaging ability. PLGA nanobubbles show good stability, high-efficiency coating, stable loading, small size, and controlled and efficiency release. Wheatley et al. [49] developed a surfactant-stabilized UCA by differential centrifugation method at a speed of 300 rpm for 3 min. The UCA had an average diameter of 450 nm, which gave 25.5 dB enhancements in vitro at a dose of 10 microL/mL (with a half-life of 13 min). Moreover, the UCA produced wonderful in vivo power Doppler images and grey-scale pulse inversion harmonic images at low sound power levels. Xing et al. [47] fabricated a new kind of biocompatible nanobubbles by ultrasonication of a mixture of polyoxyethylene 40 stearate (PEG 40S) and Span 60 followed by differential centrifugation method. The nanobubbles had a precisely controlled mean size which was small enough to permeate through tumor cell membrane. The differential centrifugation method was an effective method for size separation of particles. It produced narrow size distributions for certain applications. Under the protection of perfluoropropane gas, the bubbles remained stable for more than two weeks. The acoustic behavior of the nanosized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. The figure showed an example of the reflectivity enhancement by comparing two images, at the beginning of the injection and at the maximum enhancement after injection, respectively. The image appeared black due to no nanobubbles (Figure 2(a)); however, when the nanobubbles were injected in rabbit, marked and complete power Doppler enhancement appeared immediately following slow infusion of the contrast agent and color flare appeared in the renal parenchyma (Figure 2(b)). In vivo power Doppler imaging (PDI) enhancement was observed for about 1 min, suggesting such nanobubbles were stable enough for ultrasound imaging. At the condition of 20 g sample (for 5 min), the maximum enhancement was not observed in PDI modes. This was most likely because of differences in the concentration and stability of the nanobubbles. The imaging observation along with the precipitations for 5 min samples assuredly pointed to better stability for the 3 min samples. According to the experiments, the 3 min and 20 g sample seemed to be the most promising choice for tumor imaging and US-mediated targeted therapy. Yin et al. [48] developed the US-sensitive siRNA-nanobubbles (NBs, referred to as gas-cored liposomes) for tumor imaging and targeted drug delivery. Effective accumulation of the nanobubbles in tumor tissues could be achieved via the EPR effect. The changes of gray-scale intensities before and after US exposure showed that the siRNA-NBs had good US sensitivity, which hold great potential for US-mediated in vivo therapy for tumors. According to the further results, the gray-scale intensities of siRNA-NBs decreased more slowly than the gas-cored liposomes (Figure 2(c)), suggesting good stability; moreover, low-frequency US triggered similarly prompt decrease in gray-scale intensity for both the siRNA-NBs and the liposomes, suggesting that siRNA micelle adhering to liposome surfaces did not alter the sensitivity of the liposomes to ultrasound. With the aid of low-frequency US exposure, siRNA micelles were released from the siRNA-NBs and delivered into tumor cells. Wang et al. [3] used coumarin as a model drug loaded into nanobubbles to investigate the drug delivery potential to cells. The results showed that the nanobubbles (composed of 1% of Tween 80, 3 mg/mL of lipid) presented best in vivo imaging of liver.

Bottom Line: These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy.The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle.In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

View Article: PubMed Central - PubMed

Affiliation: Department of Ultrasound Medicine, Laboratory of Ultrasound Molecular Imaging, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China.

ABSTRACT
With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

Show MeSH
Related in: MedlinePlus