Near-infrared light-triggered NO release for spinal cord injury repair

Abstract

Traumatic spinal cord injury (SCI) is caused by external physical impacts and can induce complex cascade events, sometimes converging to paralysis. Existing clinical drugs to traumatic SCI have limited therapeutic efficacy because of either the poor blood–spinal cord barrier (BSCB) permeability or a single function. Here, we suggest a “pleiotropic messenger” strategy based on near-infrared (NIR)–triggered on-demand NO release at the lesion area for traumatic SCI recovery via the concurrent neuroregeneration and neuroprotection processing. This NO delivery system was constructed as upconversion nanoparticle (UCNP) core coated by zeolitic imidazolate framework–8 (ZIF-8) with NO donor (CysNO). This combined strategy substantial promotes the repair of SCI in vertebrates, ascribable to the pleiotropic effects of NO including the suppression of gliosis and inflammation, the promotion of neuroregeneration, and the protection of neurons from apoptosis, which opens intriguing perspectives not only in nerve repair but also in neurological research and tissue engineering.

An injectable, self-healing, electroconductive extracellular matrix-based hydrogel for enhancing tissue repair after traumatic spinal cord injury

“…Several strategies, including stimulation of cell differentiation and neurite growth for neuroregeneration, as well as neuroprotective inflammation, are key points for the efficient repair of traumatic SCI. Nevertheless, these current treatments are effective in only one aspect of this complex and multifaceted disease, and have only limited therapeutic efficacy [ 4 ]. Therefore, new multifunctional therapeutic strategies with advanced therapeutic efficacy are being actively pursued [ 5 ].…”

Recent advances in upconversion nanoparticle-based nanocomposites for gas therapy

“…3c ). 29 This functional nanoplatform was designed with UCNPs coated with zeolitic imidazolate framework-8 (ZIF-8), which could load NO donor nitrosothiol (CysNO) by the large pore size and pore surface area. The UCL ability of UCNPs breaks the S–NO bonds of CysNO to release NO after irradiation with NIR light, followed by a slow increase in NO level.…”

“…, gas chromatography, Griess assay, and gas microelectrode), can be used to monitor the gas concentration in tissues in real-time, and thus can control the power and distance of the excited light. 23,24,29 Therefore, the development and application of UCNP-based nanocomposites to realize the controlled release of therapeutic gases are greatly desired. However, there is no systematic summary of UCNP-based gas therapies to guide bio-application in the literature.…”

Restoring Sensorimotor Function Through Neuromodulation After Spinal Cord Injury: Progress and Remaining Challenges

“…In addition, a UCNP-based multi-effect messenger strategy combined to NIR that triggers the release of nitric oxide in the damaged area on demand has been proposed. UCNPs were constructed for the vector to achieve the recovery of traumatic SCI through simultaneous nerve regeneration and neuroprotection processes, which inhibit glial cell inflammation and promote regeneration (Jiang et al, 2020 ).…”