| Summary: | Traumatic brain injury (TBI) is one of the major risk factors for disability and death affecting people of all age groups. Secondary TBI injuries can potentially deteriorate and cause progressive neurodegeneration and neurological disability. Although secondary TBI injuries can be potentially prevented, currently, there are still no effective neuroprotective therapeutics that can minimize their detrimental effects due to the heterogeneity and complexity of the pathological mechanisms that ensue after brain injury. It was hypothesized that successful delivery of intact functional microRNA-124 (miR124) could potentially help ameliorate TBI-induced secondary injuries by reducing neuroinflammation, preserving cell survival, and stimulating regeneration after injury. To harness the neuroprotective potential of miR124, this study engineered a wheat germ agglutinin (WGA)-conjugated polymer NP that can be loaded with miR124 (WGA-NP-miR124) and evaluated its therapeutic properties in vitro. Characterization studies indicated that WGA-NP-miR124 possesses the ideal physical and chemical characteristics for intranasal delivery. In vitro cellular model experiments showed that WGA-NP-miR124 has no significant cytotoxicity and can be efficiently taken up by cells. Treatment of the SH-SY5Y scratch injury model with WGA-NP-miR124 significantly improved cell proliferation after injury. The protein expression level of the PARP p85 fragment and the results of the apoptosis assay indicated that WGA-NP-miR124 treatment reduced cell death and enhanced cell proliferation. Overall, these findings in vitro suggest that WGA-NP-miR124 holds promising therapeutic effects in enhancing cell proliferation and inhibiting apoptosis, which could benefit future TBI treatment approaches.
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