Dual-function hybrid nanoparticles with gene silencing and anti-inflammatory effects

Background: 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.

Aim: To design and test a hybrid nanocarrier with the capacity to lower Huntington’s Disease gene (HTT) expression and prevent or diminish inflammation.

Methods: 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.

Results: 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 HTT gene expression and reduced levels of expression of the proinflammatory cytokine IL-6.

Conclusion: A novel hybrid nanocarrier system with dual actions is effective in lowering HTT gene expression and attenuating inflammatory processes.