Article

Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure.

Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa, Japan.
Journal of Controlled Release (impact factor: 5.73). 10/2009; 142(2):245-50. DOI:10.1016/j.jconrel.2009.10.027 pp.245-50
Source: PubMed

ABSTRACT Interleukin-12 (IL-12) gene therapy is expected to be effective against cancers because it primes the immune system for cancer cells. In this therapy, it is important to induce IL-12 gene expression in the tumor tissue. Sonoporation is an attractive technique for developing non-invasive and non-viral gene delivery systems, but simple sonoporation using only ultrasound is not an effective cancer gene therapy because of the low efficiency of gene delivery. We addressed this problem by combining ultrasound and novel ultrasound-sensitive liposomes (Bubble liposomes) which contain the ultrasound imaging gas perfluoropropane. Our previous work showed that this is an effective gene delivery system, and that Bubble liposome collapse (cavitation) is induced by ultrasound exposure. In this study, we assessed the utility of this system in cancer gene therapy using IL-12 corded plasmid DNA. The combination of Bubble liposomes and ultrasound dramatically suppressed tumor growth. This therapeutic effect was T-cell dependent, requiring mainly CD8(+) T lymphocytes in the effector phase, as confirmed by a mouse in vivo depletion assay. In addition, migration of CD8(+) T cells was observed in the mice, indicating that the combination of Bubble liposomes and ultrasound is a good non-viral vector system in IL-12 cancer gene therapy.

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Keywords

attractive technique
 
Bubble liposome collapse
 
Bubble liposomes
 
cancer cells
 
cancer gene therapy
 
cancers
 
effective cancer gene therapy
 
effective gene delivery system
 
effector phase
 
good non-viral vector system
 
IL-12 cancer gene therapy
 
IL-12 corded plasmid DNA
 
induce IL-12 gene expression
 
non-viral gene delivery systems
 
novel ultrasound-sensitive liposomes
 
simple sonoporation
 
therapeutic effect
 
tumor tissue
 
ultrasound exposure
 
ultrasound imaging gas perfluoropropane