In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury

Abstract

The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology of SCI, leading to scant treatment efficacies. Here, we developed a facile in situ reaction-induced self-assembly method to prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined neuroprotection in SCI. The prepared PFCN could release PAH and curcumin in response to oxidative and acidic SCI microenvironment. Subsequently, PFCN exhibited an effectively neuroprotective effect through scavenging toxic aldehydes as well as reactive nitrogen and oxygen species in neurons, modulating microglial M1/M2 polarization, and down-regulating the expression of inflammation-related cytokines to inhibit neuroinflammation. The intravenous administration of PFCN could significantly ameliorate the malignant microenvironment of injured spinal cord, protect the neurons, and promote the motor function recovery in the contusive SCI rat model.

Acid Neutralization by Composite Lysine Nanoparticles for Spinal Cord Injury Recovery through Mitigating Mitochondrial Dysfunction

“…A study by Yuan et al utilized epigallocatechin gallate (EGCG) nanoparticles to effectively suppress the inflammatory response and mitigate ROS, thereby exerting a neuroprotective effect . Similarly, Liu et al prepared aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named PFCN), which released curcumin and PAH under acidic and oxidative microenvironmental conditions, thereby achieving the clearance of inflammatory factors, ROS, and aldehydes, providing synergistic multifactorial regulation for SCI repair . Zhu et al constructed high deferoxamine loading nanoparticles, and demonstrated excellent scavenging performance in iron-overloaded cell model and energetically exhibited neural cell protection …”