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In order to create a technology that is relevant for siRNA delivery in TBI after systemic administration, sub\u2010100\u00a0nm nanoparticles with rolling circle transcription (RCT) are synthesized and isolated in order improve payload delivery into the injured brain. Unlike conventional RCT\u2010based RNA particles, in this method, sub\u2010100\u00a0nm RNA nanoparticles (RNPs) are isolated. To enhance RNP pharmacokinetics, RNPs are synthesized with modified bases in order to graft polyethylene glycol (PEG) to the RNPs. PEGylated RNPs (PEG\u2010RNPs) do not significantly impact their knockdown activity in vitro and lead to longer blood half\u2010life after systemic administration and greater accumulation into the injured brain in a mouse model of TBI. In order to demonstrate RNA interference (RNAi) activity of RNPs, knockdown of the inflammatory cytokine TNF\u2010\u03b1 in injured brain tissue after systemic administration of RNPs in a mouse model of TBI is demonstrated. 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