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Key Analysis
I. Research Background
After spinal cord injury (SCI), neutrophil extracellular traps (NETs) exacerbate secondary damage and hinder nerve regeneration; while brain-derived neurotrophic factor (BDNF) can promote repair, it faces challenges such as difficult delivery and poor stability. How to simultaneously remove NETs and target delivery of BDNF has become the key to treatment.
II. Core Innovation Points
▪ Bionic Membrane Targeted Delivery System: Utilizing activated microglial cell membranes to coat nanoparticles, achieving long-term circulation and targeted enrichment at the inflammatory site (see Fig 1a, 4b–e).
▪ NETs Clearance and Immune Regulation: The membrane surface polySia efficiently binds NETs and activates phagocytosis by exposing phosphatidylserine (PS), significantly reducing pro-inflammatory responses (see Fig 2, 5).
▪ Microenvironment Triggered Drug Release: In the acidic microenvironment at the injury site, the core of the nanoparticles reverts to natural BDNF, promoting neurite growth and myelin repair (see Fig 3g, 6).
III. Research Logical Chain
Construct ATP-modified BDNF nanoparticles (A-BDNF NPs) → Coat polySia-expressing microglial cell membranes (PBM) to form INPT → After intravenous injection, they target and accumulate in the spinal cord injury area → PolySia binds to NETs and induces membrane detachment → Exposure of PS signals initiates phagocytosis to remove NETs → Acidic microenvironment triggers BDNF release → Synergistically achieve anti-inflammatory and nerve regeneration.
IV. Scientific Insights
This study demonstrates a "immune regulation + nerve regeneration" dual-effect integrated nanotherapy strategy, providing a new treatment platform for spinal cord injury and other central nervous system diseases (such as stroke, neurodegenerative diseases). Its bionic membrane design, microenvironment-responsive release mechanism, and NETs clearance pathway also bring new ideas for targeted delivery and immune engineering research.
Paper Link (doi): https://doi.org/10.1002/adma.202518580
