The present paper reports the utilization of hybrid nanocomposite particles consisting of PEI25k-PEG5k copolymer grafted silica nanoparticles (SiO2NPs) for enhanced cellular uptake and siRNA delivery. High-resolution transmission electron microscopy and dynamic light scattering measurements ensured the average particle size of the final hybrid component as 45 nm (core SiO2, 28–30 nm and shell PEI25k-PEG5k, 12–15 nm). Surface morphology from atomic force microscopy analysis showed the significant relationship between the particle size and shape. 29Si and 13C cross-polarization–magic angle spinning solid state nuclear magnetic resonance (NMR), 1H-NMR, and Fourier transform infrared spectroscopy were used to obtain the relevant structural information (such as Q3, silanol; Q4, siloxane functional groups of SiO2NPs; resonance shifts and bending vibrations of PEI25k, –CH2–CH2–NH–; and PEG5k, –CH2–CH2–O–) from copolymer nanoparticle. Stable complexation of siRNA and nanocomposite particle (wt.%:wt.%) was achieved from 1:5 to 1:15 ratio. Nanocomposite particle (N/P) ratio and siRNA concentration determine the stability and knockdown efficiency of the PEI25k-PEG5k-graft-SiO2NPs–siRNA complexes. It was shown that highly positively charged (zeta potential, +66 mV) PEI25k-PEG5k-graft-SiO2NPs result in strong affinity with negatively charged siRNA. Confocal microscopy showed intensified cellular uptake of siRNA into cytoplasm of A549 cancer cell utilized for in vitro study. In conclusion, the coherence, graft density of copolymer-SiO2NPs, and siRNA concentration were found to strongly influence the stability, and hence determine the knockdown efficiency, of PEI25k-PEG5k-graft-SiO2NPs–siRNA complexes.
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This study was supported by a grant of the Ministry of Health and Welfare (A040041) and Samsung Biomedical Research Institute, Republic of Korea (PB00021). We thank Ms. Yunhee Kim for solid NMR spectroscopic analysis in NICEM, SNU, and Ms. Youngshin Yoo for HR-TEM analysis in SKKU.