Phospholipid-Coated Guanosine Diphosphate Auxiliary CaP Active Nanoparticles Can Systematically Improve the Efficiency of Gene Therapy for Cancer Disease.

Abstract

Endogenous active substance guanosine diphosphate (GDP) is involved in the physiological process of DNA transfection and expression in the cytoplasm by binding to Ran proteins. To substantially improve the gene delivery efficiency of nanoparticles, phospholipid-coated Ca(P-GDP)/pDNA/NLS hybrid nanoparticles were prepared using GDP as a common biophosphorus source based on the biological process of exogenous gene expression in the cells. This nanoparticle has a relative uniform particle size distribution and in vitro stability. The addition of GDP in nanoparticles significantly enhanced the gene expression efficiency with good biocompatibility. Moreover, an in vivo study further verified that hybrid nanoparticles were more effective in increasing the p53 gene expression, thus significantly inhibiting the tumor growth in the heterotopic tumor model of nude mice. These results demonstrated that phospholipid-coated Ca(P-GDP) nanoparticles were a potential nonviral gene vector to promote gene expression. The experimental results confirmed the feasibility of designing a delivery system based on active substances and provided a new solution to improve the transfection efficiency of gene drugs.