Advances in nanotherapeutic strategies for Huntington's disease: Design, delivery, and neuroprotective mechanisms

Huntington's Disease (HD) is a severe neurodegenerative disorder lacking effective diagnostic and treatment options. However, there is increasing interest in the potential of nanotherapeutics to address this challenging condition. Nanotherapeutics, characterized by their distinct capacity for precise targeting and delivery of therapeutic agents to designated sites, exhibit considerable potential in the treatment of HD by addressing intricate molecular pathways. By utilizing different nanocarriers, nanotherapeutics can efficiently navigate the blood-brain barrier (BBB) and deliver therapeutic payloads directly to affected regions of the HD brain, thereby mitigating adverse effects and enhancing treatment efficacy. This review comprehensively addresses complexities associated with drug delivery to the HD-affected brain. Furthermore, it explores the design of various nanotherapeutics, elucidating the mechanism of therapeutic delivery to the brain, and their therapeutic effects in HD models. Moreover, the potential of nanotherapeutics as diagnostics in HD therapy is also explored. Despite extant challenges, such as the imperative for stringent safety assessments and the absence of FDA-endorsed nanotherapeutics for HD, the rapid progress in nanotherapeutic research unveils a diverse array of prospects capable of revolutionizing HD treatment.