Abstract
This paper focuses on novel approaches in the field of nanotechnology-based carriers utilizing ultrasound stimuli as a means to spatially target gene delivery in vivo, using nanoparticles made with either poly(lactic-co-glycolic acid) (PLGA) or other polymers. We specifically discuss the potential for gene delivery by particles that are echogenic (amenable to destruction by ultrasound) composed either of polymers (PLGA, polystyrene) or other contrast agent materials (Optison, SonoVue microbubbles). The use of ultrasound is an efficient tool to further enhance gene delivery by PLGA or other echogenic particles in vivo. Echogenic PLGA nanoparticles are an attractive strategy for ultrasound-mediated gene delivery since this polymer is currently approved by the US Food and Drug Administration for drug delivery and diagnostics in cancer, cardiovascular disease, and also other applications such as vaccines and tissue engineering. This paper will review recent successes and the potential of applying PLGA nanoparticles for gene delivery, which include (a) echogenic PLGA used with ultrasound to enhance local gene delivery in tumors or muscle and (b) PLGA nanoparticles currently under development, which could benefit in the future from ultrasound-enhanced tumor targeted gene delivery.
Highlights
To achieve successful gene therapy in a clinical setting, it is critical that gene delivery systems be safe and easy to apply and provide therapeutic transgene expression
A variety of nonviral delivery systems that can be used in different clinical settings are available and one promising direction is the development of biodegradable, echogenic nanoparticle systems that can deliver DNA efficiently by the use of ultrasound-mediated delivery
A relatively novel strategy for gene and drug delivery enhancement is application of echogenic nanoparticles made of poly(d,l-lactic-co-glycolide) (PLGA) or derivatives in combination with relatively low-intensity ultrasound (US)
Summary
To achieve successful gene therapy in a clinical setting, it is critical that gene delivery systems be safe and easy to apply and provide therapeutic transgene expression. Many studies using viral vectors have established the gold standard for successful gene transfer and high-level expression in target cells. The upcoming trend is in the development of improved methods for nonviral gene transfer, due to the considerable immunogenicity related to the use of viruses. Several novel nonviral vectors have been developed that approach viruses with respect to transfection efficiency. A variety of nonviral delivery systems that can be used in different clinical settings are available and one promising direction is the development of biodegradable, echogenic nanoparticle systems that can deliver DNA (or drugs) efficiently by the use of ultrasound-mediated delivery. We will focus our discussion on PLGA nanoparticles and their promise for nucleic acid delivery in vivo using ultrasound-mediated gene delivery methods
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