Targeted Delivery of Acid-Responsive Rutin Nanoparticles Based on Aldehyde Adsorption for the Treatment of Spinal Cord Injury in Rats

Spinal cord injury (SCI) can cause irreversible nerve damage, imposing a significant burden on both patients and society. Methylprednisolone (MP), the recommended clinical drug, possesses antioxidant, anti-inflammatory, and antiapoptotic effects. It improves nerve damage by inhibiting secondary pathological processes. However, high-dose MP administration may result in side effects, including diabetes, femoral head necrosis, and infections. Therefore, there is a need to identify safer alternatives to mitigate the issues associated with MP administration. Rutin, a natural small molecule, exhibits multifaceted therapeutic capabilities and high biosafety, making it a promising alternative to MP treatment. However, its poor solubility and rapid metabolism limit its <i>in vivo</i> bioavailability. In this study, a drug-free polypeptide (PAH) containing hydrazide groups on the side chains is designed, which can be used for mitigating secondary SCI through scavenging toxic aldehydes. Then, we utilize PAH to encapsulate rutin and develop aldehyde-responsive nanomedicine for intravenous administration in SCI rats, providing a novel approach for the clinical replacement of MP.