Pathogenesis Activated “In Situ Disassembly-Reassembly” Pattern Dual-Scavenges Cell-Free DNA/ROS for Hemorrhagic Stroke Management

Abstract

Intracerebral hemorrhage (ICH) causes uncontrolled neuroinflammation/oxidative stress to aggravate secondary brain injury (SBI) for high mortality and disability but lacks effective pharmacotherapy in clinical practices. This represents an imperative need to discover potential targets and develop advanced therapeutic strategies. Herein, it is discovered that cell-free DNA (cfDNA, a driving factor of inflammation) level in serum positively correlates with SBI severity and it is speculated as a potential targeting molecule. However, traditional cfDNA-scavenging materials are mainly limited within the polycationic type and exist severe side effects. Herein, this work designs a drug delivery nanosystem, which utilizes a pathogenesis-activated sequential disassembly-reassembly process to in situ dual-scavenge cfDNA and ROS for the regulation of neuroinflammation/oxidative stress, thereby reducing SBI and preventing further damage in experimental mice. The findings not only demonstrate the importance of cfDNA in SBI but also provide an advanced pharmacotherapy to enhance therapeutic potential toward the effective alleviation on SBI following ICH.