Dual-Function Hybrid Nanoparticles with Gene Silencing and Anti-Inflammatory Effects

Abstract

<b>Background:</b> Nanocarriers loaded with siRNA can be administered intranasally to provide a noninvasive, safe alternative to direct intracerebral or intrathecal infusions. Dual-function nanocarriers can also be designed to deliver several payloads that address different components of the pathological process. <b>Aim:</b> To design and test a hybrid nanocarrier with the capacity to lower Huntington's Disease gene (<i>HTT</i>) expression and prevent or diminish inflammation. <b>Methods:</b> Novel hybrid nanoparticles were fabricated using a chitosan-based matrix core loaded with siRNA and an outer shell consisting of a lipid composition containing cannabidiol. <b>Results:</b> Incubation of hybrid nanoparticles in mesenchymal stem cell cultures obtained from a YAC128 transgenic mouse modeling Huntington's disease resulted in effective lowering of mutant <i>HTT</i> gene expression and reduced levels of expression of the proinflammatory cytokine IL-6. <b>Conclusion:</b> A novel hybrid nanocarrier system with dual actions is effective in lowering <i>HTT</i> gene expression and attenuating inflammatory processes.