pH-sensitive nano-crystals of carbonate apatite regulate delivery and release kinetics of DNA for efficient expression in mammalian cells

摘要

Due to some major limitations of viral-mediated delivery, non-viral synthetic systems have become increasingly desirable. However, synthetic systems are notably inefficient compared to the viral ones in gene delivery and expression. Here we report on the development of the simplest, but highly efficient gene delivery device based on generated nano-apatite crystals having high affinity to DNA but fast dissolution kinetics in acidic vesicles, following efficient endocytosis, for effective release of DNA and thus result in 5 to 100-fold higher transgene expression than the existing ones. Fluoride (F-) or strontium (Sr{sup}(2+)) which is known to decrease the solubility of carbonate apatite, dramatically reduced the transfection efficiency, suggesting that DNA release through particle dissolution, is a crucial factor in gene delivery pathway. Additionally, flexibility in modulating crystal dissolution kinetics enabled to control intracellular DNA release and an intermediate rate of DNA release enhanced survival of DNA and subsequent expression.