Organelle-Targeted Nanotherapeutics for Parkinson's Disease: From Pathogenesis to Preclinical Strategies and Translational Challenges.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the aggregation of αSynuclein (αSyn). Organelle dysfunction is recognized as a central driver of pathological feature. Current treatments primarily alleviate symptoms but fail to halt disease progression, largely due to the inability to target the underlying subcellular pathology. This narrative review examines the emerging potential of organelle-targeted nanotherapeutics as a precision medicine strategy for PD treatment. We discuss how engineered nanoparticles can be designed to deliver therapeutics specifically to dysfunctional mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus, and nuclei. These approaches aim to interfere with key pathological mechanisms ameliorating oxidative stress, mitigating protein misfolding, restoring protein homeostasis, and modulating gene expression. We provide a comprehensive overview of recent preclinical advances in nanoparticles design, targeting mechanisms, and therapeutic efficacy. Furthermore, we critically evaluate the current challenges, including delivery efficiency, safety, reproducibility, storage, and large-scale translation before clinical application This review aims to provide a potential route toward disease-modifying nanotherapeutics for PD.