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Abstract: The calcium phosphate (CaP) particles have attracted much attention in gene therapy. How to construct stable gene particles was the determining factor. In this study, hybrid multi-shell CaP gene particles were successfully constructed. First, CaP nanoparticles served as a core and were coated with DNA for colloidal stabilization. The ξ-potential of DNA-coated CaP nanoparticles was −15 mV. Then polyethylenimine (PEI) was added and adsorbed outside of the DNA layer due to the electrostatic attraction. The ξ-potential of hybrid multi-shell CaP particles was slightly positive. With addition of PEI, the hybrid multi-shell particles could condense DNA effectively, which was determined by ethidium bromide (EtBr) exclusion assay. The hybrid particles were spherical and uniform with diameters of about 150 nm at proper conditions. By simple modification of PEI, the hybrid multi-shell CaP gene particles were successfully constructed. They may have great potential in gene therapy.

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