Therapeutic siCCR2 Loaded by Tetrahedral Framework DNA Nanorobotics in Therapy for Intracranial Hemorrhage

Modulating microglial polarization is a potential strategy to assuage secondary brain injury caused by intracranial hemorrhage (ICH). However, despite decades of effort, effective therapies targeting microglia for ICH are still lacking. Here, a nanorobotic, tetrahedral framework nucleic acid (tFNA), is successfully synthesized and designed to carry C-C chemokine receptor 2 (siCCR2) for use in in vitro hemin-induced and in vivo collagenase-induced ICH models. This nanoscale complex (tFNA-siCCR2), which possesses biocompatibility, editability, and structural stability, exhibits a favorable effect in inhibiting the expression of CCR2. After treatment with tFNA-siCCR2, hematoma absorption is accelerated, and neurological inflammation is mitigated by decreasing levels of proinflammatory cytokines, while increasing the release of anti-inflammatory factors. Consequently, the neurological deficits of mice with ICH improve. These results indicate that inhibiting CCR2 expression during the acute phase of ICH polarizes microglia towards a therapeutic subtype, and restores neurological function, which demonstrates that tFNA has a promising ability to transfer siCCR2 for treating ICH.