We propose an effective siRNA delivery system by preparing poly(DAMA-HEMA)-multilayered gold nanoparticles using multiple surface-initiated atom transfer radical polymerization processes. The polymeric multilayer structure is characterized by transmission electron microscopy, matrix-associated laser desorption/ionization time-of-flight mass spectrometry, UV-vis spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and ζ-potential. The amount of siRNA electrostatically incorporated into the nanoparticle can be tuned by the number of polymeric shells, which in turn influences the cellular uptake and gene silencing effect. In a bioreductive environment, the interlayer disulfide bond breaks to release the siRNA from the degraded polymeric shells. Intravenously injected c-Myc siRNA-incorporated particles accumulate in the tumor site of a murine lung carcinoma model and significantly suppress the tumor growth. Therefore, the combination of a size-tunable AuNP core and an ATRP-functionalized shell offers control and versatility in the effective delivery of siRNA.
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