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Designing multifunctionalized selenium nanoparticles to reverse oxidative stress-induced spinal cord injury by
Siyuan Rao1, Yongpeng Lin, Yanxin Du
1Guangzhou University of Chinese Medicine, Guangzhou, China.
Abstract:
Spinal cord injury (SCI) remains a challenging clinical problem worldwide, due to the lack of effective drugs for precise treatment. Among the complex pathophysiological events following SCI, reactive oxygen species (ROS) overproduction plays a particularly significant role. As therapeutic agents for neurological diseases, tetramethylpyrazine (TMP) and monosialotetrahexosylganglioside (GM1) have been widely used in the clinical treatment of SCI. Our previous studies have reported that functionalized selenium nanoparticles (SeNPs) exhibit excellent antioxidant activity against oxidative stress-related diseases. Therefore, in this study, novel multifunctionalized SeNPs decorated with polysaccharide-protein complex (PTW)/PG-6 peptide and loaded with TMP/GM1 were rationally designed and synthesized, which exhibited a satisfactory size distribution and superior stability. Furthermore, the protective effects of SeNPs@GM1/TMP on PC12 cells against tert-butyl hydroperoxide (t-BOOH)-induced cytotoxicity and the underlying mechanisms were also explored. Flow cytometric analysis indicated that SeNPs@GM1/TMP showed strongly protective effects against t-BOOH-induced G2/M phase arrest and apoptosis. Moreover, we found that SeNPs@GM1/TMP could attenuate ROS overproduction to prevent mitochondria dysfunction via inhibiting the activation of p53 and MAPK pathways. Effects of SeNPs@GM1/TMP on functional recovery after SCI were evaluated by the Basso-Beattie-Bresnahan (BBB) locomotion scale, inclined plane test, and footprint analysis. The results of hematoxylin-eosin staining and Nissl staining also showed that SeNPs@GM1/TMP provided a neuroprotective effect in SCI rats. This finding suggests that SeNPs@GM1/TMP could be further developed as a promising nanomedicine for efficient SCI treatment.
Insights
This study developed novel selenium nanoparticles (SeNPs) loaded with tetramethylpyrazine (TMP) and monosialotetrahexosylganglioside (GM1) to treat spinal cord injury (SCI). The nanomedicine protected cells from damage and improved functional recovery in SCI rats.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Neuroscience
Background:
- Spinal cord injury (SCI) presents a significant global health challenge due to limited effective treatments.
- Overproduction of reactive oxygen species (ROS) is a key factor in SCI pathophysiology.
- Tetramethylpyrazine (TMP) and monosialotetrahexosylganglioside (GM1) are clinically used for neurological diseases, while selenium nanoparticles (SeNPs) show antioxidant properties.
Purpose of the Study:
- To design and synthesize multifunctionalized SeNPs loaded with TMP/GM1 for potential SCI treatment.
- To evaluate the protective effects of these nanoparticles against oxidative stress-induced cell damage.
- To investigate the therapeutic efficacy of the nanoparticles in a rat model of SCI.
Main Methods:
- Synthesis of SeNPs decorated with polysaccharide-protein complex (PTW)/PG-6 peptide and loaded with TMP/GM1.
- Assessment of nanoparticle characteristics (size, stability).
- In vitro evaluation of protective effects on PC12 cells against tert-butyl hydroperoxide (t-BOOH) using flow cytometry.
- In vivo assessment of functional recovery in SCI rats using BBB locomotion scale, inclined plane test, and footprint analysis.
- Histological analysis (H&E and Nissl staining) of spinal cord tissue.
Main Results:
- The synthesized SeNPs@GM1/TMP exhibited desirable size distribution and stability.
- SeNPs@GM1/TMP demonstrated significant protection against t-BOOH-induced cytotoxicity, G2/M phase arrest, and apoptosis in PC12 cells.
- The nanoparticles attenuated ROS overproduction and prevented mitochondrial dysfunction by inhibiting p53 and MAPK pathways.
- In vivo studies showed improved functional recovery in SCI rats treated with SeNPs@GM1/TMP.
- Histological analysis confirmed neuroprotective effects of SeNPs@GM1/TMP in SCI rat models.
Conclusions:
- Multifunctionalized SeNPs@GM1/TMP effectively protect against oxidative stress and neuronal damage.
- This novel nanomedicine demonstrates potential for enhancing functional recovery after spinal cord injury.
- SeNPs@GM1/TMP represent a promising therapeutic candidate for future development in SCI treatment.
