Engineering small MgAl-layered double hydroxide nanoparticles for enhanced gene delivery

•Control preparation of smaller layered double hydroxide (sLDH) nanoparticles.•The number-average size of sLDH particles can be as smaller as 15–20 nm.•Detail investigation of experimental factors on the sLDH size and distribution.•Enhanced sLDH nanoparticle-mediated gene delivery.

In this paper we report an approach for engineering small MgAl-layered double hydroxide (sLDH) nanoparticles with the Z-average diameter of about 40 nm. This method first requires co-precipitation of magnesium and aluminum nitrate solution with sodium hydroxide in methanol, followed by LDH slurry collection and re-suspension in methanol. The methanol suspension is then heated in an autoclave, followed by separation via centrifugation and thorough washing with deionized water. The nanoparticles are finally dispersed in deionized water into homogeneous aqueous suspension after 4–6 day standing at room temperature. In general, sLDH nanoparticles have the Z-average size of 35–50 nm, the number-average size of 14–30 nm and the polydispersity index (PdI) of 0.19–0.25. The prepared sLDH suspension is stable for at least 1 month when stored at fridge (2–8 °C) or ambient (22–25 °C) temperature. Moreover, sLDH nanoparticles are found to carry higher payloads of small double stranded DNA (dsDNA). More excitedly, sLDH nanoparticles transfect dsDNA into HEK 293T cells with a 5 to 6-fold greater efficiency compared to the larger LDH particles (Z-average diameter of 110 nm).

Graphical abstractSmall LDH nanoparticles are reproducibly prepared by non-aqueous coprecipitation method. The resultant small LDH nanoparticles possess a narrow particle size distribution with a Z-average diameter size of ~ 40 nm and a hexagonal morphology. Such small LDH nanoparticles can carry more double stranded DNA and more efficiently transfect to HEK 293T cells than normal LDH particles (Z-average diameter size of ~ 110 nm).Figure optionsDownload full-size imageDownload as PowerPoint slide