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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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Injection-induced droplet-to-bubble transition. (a) Nanodroplets inserted in PBS through an 18 G needle or 26 G needle. Bubbles formed when nanoemulsion was injected through a thin needle are seen as bright spots (indicated by arrows in the right panel); bubbles rise to the surface while droplets precipitate to the bottom of a test tube. (b) Nanodroplets injected in the agarose gel 18 G (left) or 26 G (right) needles. Injection through the 18 G needle leads to very bright bubbles instantly, whose brightness and size increase over time; the increased brightness of the droplets with time suggesting a droplet-to-bubble transition [53].
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fig3: Injection-induced droplet-to-bubble transition. (a) Nanodroplets inserted in PBS through an 18 G needle or 26 G needle. Bubbles formed when nanoemulsion was injected through a thin needle are seen as bright spots (indicated by arrows in the right panel); bubbles rise to the surface while droplets precipitate to the bottom of a test tube. (b) Nanodroplets injected in the agarose gel 18 G (left) or 26 G (right) needles. Injection through the 18 G needle leads to very bright bubbles instantly, whose brightness and size increase over time; the increased brightness of the droplets with time suggesting a droplet-to-bubble transition [53].

Mentions: The family of liquid perfluorocarbons (PFCs) includes Perfluorodecalin (PFD), Perfluorooctyl bromide (PFOB), Perfluorohexane (PFH), Perfluoropentane (PFP), Perfluorotributylamine (PFTBA), and Perfluoro-15-crown-5-ether (PFCE). PFCs are fluorinated compounds that have been used for many years in clinics mainly as gas/oxygen carriers and for liquid ventilation. Besides this main application, PFCs have also been tested as contrast agents for ultrasonography and magnetic resonance imaging and targeted therapy [51]. A PFC nanoemulsion is prepared by the mixture of perfluorinated hexane and perfluorinated pentane. The nanoemulsion can be prepared by the self-assembly property of polymer and solvent replacement technology. The use of polymer materials wrapping liquid halothane (such as PFP) is a new research direction for preparing nanoemulsions. Under the effect of low-frequency ultrasound, PFH used as the core of phase-change ultrasonic molecular probe has great potential to be an ideal multifunctional agent. PFC particles can infiltrate into arterial walls after balloon injury, cross the internal elastic lamina, and bind and localize molecular epitopes in intramural tissues. Similar PFC nanoparticles targeted to markers of angiogenesis had been successfully used to detect neovasculature around tumors implanted in athymic nude mice using a research ultrasound scanner [52]. Rapoport et al. [53] prepared paclitaxel-loaded perfluorocarbon nanoemulsions stabilized by biodegradable amphiphilic block copolymers, which were systemically injected into mouse models, leading to efficient tumor regression in pancreatic, ovarian, and breast cancer models under the action of ultrasound (1 MHz). Block-copolymer shells of nanoemulsions provide for good in vivo stability and allow enhanced accumulation in the tumor via the EPR effect and the possible active targeting. The drug-loaded perfluorocarbon nanoemulsions could convert into microbubbles locally under the action of ultrasound, resulting in a 125-fold increase of volume and a 25-fold increase of surface area. This in turn resulted in a 25-fold decrease of the primary thickness of the shell. This significantly increased the surface area of copolymer molecule. The droplet-to-bubble transition and bubble oscillation induced drug release and enhanced intracellular uptake. Stable cavitation of microbubbles might be the main mechanism of enhanced drug delivery (Figure 3).


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)

Injection-induced droplet-to-bubble transition. (a) Nanodroplets inserted in PBS through an 18 G needle or 26 G needle. Bubbles formed when nanoemulsion was injected through a thin needle are seen as bright spots (indicated by arrows in the right panel); bubbles rise to the surface while droplets precipitate to the bottom of a test tube. (b) Nanodroplets injected in the agarose gel 18 G (left) or 26 G (right) needles. Injection through the 18 G needle leads to very bright bubbles instantly, whose brightness and size increase over time; the increased brightness of the droplets with time suggesting a droplet-to-bubble transition [53].
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Related In: Results  -  Collection

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fig3: Injection-induced droplet-to-bubble transition. (a) Nanodroplets inserted in PBS through an 18 G needle or 26 G needle. Bubbles formed when nanoemulsion was injected through a thin needle are seen as bright spots (indicated by arrows in the right panel); bubbles rise to the surface while droplets precipitate to the bottom of a test tube. (b) Nanodroplets injected in the agarose gel 18 G (left) or 26 G (right) needles. Injection through the 18 G needle leads to very bright bubbles instantly, whose brightness and size increase over time; the increased brightness of the droplets with time suggesting a droplet-to-bubble transition [53].
Mentions: The family of liquid perfluorocarbons (PFCs) includes Perfluorodecalin (PFD), Perfluorooctyl bromide (PFOB), Perfluorohexane (PFH), Perfluoropentane (PFP), Perfluorotributylamine (PFTBA), and Perfluoro-15-crown-5-ether (PFCE). PFCs are fluorinated compounds that have been used for many years in clinics mainly as gas/oxygen carriers and for liquid ventilation. Besides this main application, PFCs have also been tested as contrast agents for ultrasonography and magnetic resonance imaging and targeted therapy [51]. A PFC nanoemulsion is prepared by the mixture of perfluorinated hexane and perfluorinated pentane. The nanoemulsion can be prepared by the self-assembly property of polymer and solvent replacement technology. The use of polymer materials wrapping liquid halothane (such as PFP) is a new research direction for preparing nanoemulsions. Under the effect of low-frequency ultrasound, PFH used as the core of phase-change ultrasonic molecular probe has great potential to be an ideal multifunctional agent. PFC particles can infiltrate into arterial walls after balloon injury, cross the internal elastic lamina, and bind and localize molecular epitopes in intramural tissues. Similar PFC nanoparticles targeted to markers of angiogenesis had been successfully used to detect neovasculature around tumors implanted in athymic nude mice using a research ultrasound scanner [52]. Rapoport et al. [53] prepared paclitaxel-loaded perfluorocarbon nanoemulsions stabilized by biodegradable amphiphilic block copolymers, which were systemically injected into mouse models, leading to efficient tumor regression in pancreatic, ovarian, and breast cancer models under the action of ultrasound (1 MHz). Block-copolymer shells of nanoemulsions provide for good in vivo stability and allow enhanced accumulation in the tumor via the EPR effect and the possible active targeting. The drug-loaded perfluorocarbon nanoemulsions could convert into microbubbles locally under the action of ultrasound, resulting in a 125-fold increase of volume and a 25-fold increase of surface area. This in turn resulted in a 25-fold decrease of the primary thickness of the shell. This significantly increased the surface area of copolymer molecule. The droplet-to-bubble transition and bubble oscillation induced drug release and enhanced intracellular uptake. Stable cavitation of microbubbles might be the main mechanism of enhanced drug delivery (Figure 3).

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