pH-Sensitive Inorganic Nano-Particles and Their Precise Cell Targetibility:An Efficient Gene Delivery and Expression System

Ezharul      Hoque Chowdhury; Toshihiro      Akaike

Abstract

The completion of whole human genome sequencing encourages the development of a powerful gene delivery technology for elucidating structure, regulation and function of genes and proteins in addition to the emerging biomedical applications, such as industry-based productions of therapeutic proteins and ‘gene therapy’. 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. We have recently developed the simplest, but highly efficient gene delivery device based on generated carbonate apatite nano-crystals having high affinity for DNA but fast dissolution kinetics for effective release of DNA during vesicular acidification and thus resulting in 5 to 100-fold higher transgene expression than the existing ones. Since like carbonate, Mg2+ incorporation into apatite could regulate particle size and solubility, we have also successfully designed nano-precipitates of Ca-Mg phosphate as much more efficient carriers of genetic materials than classical Ca phosphate precipitation method. Moreover, for cell-specific and more efficient transgene delivery, we successfully assembled a desirable cell-recognizable protein in the flexible manner and a highly hydrophilic protein onto the DNA/crystal surfaces, thereby creating dual surface properties, one facilitating cell-specific delivery and the other blocking non-specific interactions. Thus, considering the efficiency, celltargetability, biodegradability and simplicity, this newly developed gene delivery technology would emerge as a superior tool over the other existing ones for both basic research laboratories and clinical medicine and additionally, would enable to develop a new era for inorganic crystal-based therapeutic delivery.

Keywords: pH-sensitive, inorganic nano-particle, carbonate apatite, Ca-Mg phosphate, Ca phosphate, gene delivery, transfection, cell targeted, receptor, asialofetuin