Exploring a plasmid DNA (pDNA)/small interfering RNA (siRNA) delivery vector with excellent biocompatibility and high gene transfection efficiency still remains a great challenge. In this research, generation 5 (G5) dendrimer-entrapped gold nanoparticles (Au DENPs) partially modified with polyethylene glycol monomethyl ether (mPEG) were designed as non-viral pDNA/siRNA delivery vectors. The pDNA that can encode luciferase (Luc) or enhanced green fluorescent protein (EGFP) and the Bcl-2 siRNA that can knockdown the expression of the Bcl-2 protein were successfully packaged by the partially PEGylated Au DENPs and effectively delivered into HeLa cells. The length of the surface conjugated mPEG chains and the composition of the entrapped Au NPs were systematically altered to explore their influences on the structure, cytotoxicity, and pDNA or siRNA delivery efficiency. We show that the modified mPEG and entrapped Au NPs can significantly improve the encoding of Luc and EGFP or silence the Bcl-2 protein expression, and the {(Au)-G5.NH-mPEG2K} DENPs display the best DNA or siRNA delivery efficiency among all the designed partially PEGylated Au DENPs. The Luc transfection efficiency of the {(Au)-G5.NH-mPEG2K} was about 292 times higher than that of the G5.NH dendrimers at an N/P ratio of 5 : 1, and the Bcl-2 protein was silenced to 15% using the {(Au)-G5.NH-mPEG2K} as a vector relative to the expression level transfected using the G5.NH dendrimers (100%). With enhanced pDNA/siRNA transfection efficiency and less cytotoxicity, the PEGylated Au DENPs may hold great promise to be used in pDNA and siRNA delivery applications.
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