Info

Gene transduction i Canny wan

RBCs Delfv**Y V&vdes (LaJpMOmas) McrotxibWe»

RBCs Delfv**Y V&vdes (LaJpMOmas) McrotxibWe»

Fig. 2. Schematic representation of a method for delivering intravascular drugs or genes to tissues with microbubbles. A Intravascular microbubbles and gene-bearing vehicles flow through capillaries. B Ultrasound is applied in the target region, thereby destroying the microbubbles and permeabilizing the microvessel wall. C Intravascular gene-bearing vehicles are delivered to the tissue by convective forces. RBCs, Red blood cells

Fig. 2. Schematic representation of a method for delivering intravascular drugs or genes to tissues with microbubbles. A Intravascular microbubbles and gene-bearing vehicles flow through capillaries. B Ultrasound is applied in the target region, thereby destroying the microbubbles and permeabilizing the microvessel wall. C Intravascular gene-bearing vehicles are delivered to the tissue by convective forces. RBCs, Red blood cells

Ultrasound contrast agent microbubbles, which are typically used for image enhancement, are capable of amplifying both the targeting and the transport of drugs and genes to tissues. Microbubble targeting can be achieved by the intrinsic binding properties of the microbubble shells or through the attachment of site-specific ligands. Once microbubbles have been targeted to the region of interest, microvessel walls can be permeabilized by destroying the microbubbles with low-frequency, high-power ultrasound (Fig. 2).

A second level of targeting specificity can be achieved by carefully controlling the ultrasound field and limiting microbubble destruction to the region of interest. When microbubbles are destroyed, drugs or genes that are housed within them or bound to their shells can be released to the blood stream and then deliv-

Mcrcbubbto Bound Genes or Drugs

Mcrcbubbto Bound Genes or Drugs

Fig. 3. Schematic representation of a method for delivering intravascular drugs or genes to tissues with microbubbles that are engineered to house drugs or genes on the microbubbles. A Intravascular microbubble-bound genes or drugs flow through capillaries. B Ultrasound application to the target region destroys microbubbles, thereby per-meabilizing the microvessel walls and releasing drugs or genes into the blood stream. C Drugs or genes are delivered to tissue through permeabilized microvessels by convec-tive forces

Fig. 3. Schematic representation of a method for delivering intravascular drugs or genes to tissues with microbubbles that are engineered to house drugs or genes on the microbubbles. A Intravascular microbubble-bound genes or drugs flow through capillaries. B Ultrasound application to the target region destroys microbubbles, thereby per-meabilizing the microvessel walls and releasing drugs or genes into the blood stream. C Drugs or genes are delivered to tissue through permeabilized microvessels by convec-tive forces ered to tissue by convective forces through the permeabilized microvessels. An alternative strategy is to increase the payload volume by coinjecting drug- or gene-bearing vehicles, such as liposomes, with the microbubbles. In this manifestation, microbubbles are used for creating sites of microvessel permeabiliza-tion that facilitate drug or gene vehicle transport (Fig. 3) [25]. Azuma et al. established a novel ultrasound contrast agent-mediated gene transfection approach and demonstrated the significant prolongation of graft survival by the successful transfection of NFkappa B-decoy into the donor kidney in a rat renal allograft model [26].

The major problem with these methods is the relatively low efficiency of the gene transfer ratio compared with other methods, such as the use of virus vectors, particularly in vivo. Further, the amount of contrast agent necessary to obtain satisfactory transduction efficiency is significantly higher than that recommended for clinical use. Modification of the plasma membrane on which transient pore formation occurs influences the transduction efficiency. Local anesthetics as membrane modifiers were shown to enhance the efficiency of ultrasound-mediated gene transfection with an echo contrast agent. Local anesthetics have been shown to destabilize lipid membranes by breaking the hydration shell and fluidizing lipid membranes [27]. This enhancement effect by local anesthetics could be useful for ultrasound-mediated gene therapy in the future, since both methods of membrane modification could be directly applied to the human body.

Fig. 4. Schematic representation of high-intensity focused ultrasound (HIFU) device. Focused ultrasound was generated by a piezoelectric disc transducer, focused by a polystyrene lens, and coupled into a water tank. The reaction vials containing cells mixed with DNA were positioned in the ellipsoidal focus. For in vivo experiments, the same device was used

Fig. 4. Schematic representation of high-intensity focused ultrasound (HIFU) device. Focused ultrasound was generated by a piezoelectric disc transducer, focused by a polystyrene lens, and coupled into a water tank. The reaction vials containing cells mixed with DNA were positioned in the ellipsoidal focus. For in vivo experiments, the same device was used

Was this article helpful?

0 0

Post a comment