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

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

Journal not recorded · Published 2026-05-13

Liu,MaoYu, Peng,QiWei, Zhai,Heng, Wu,Yi, Ma,ZhuoRan, Tang,ZhiCheng, Ouyang,Haoxuan, Chang,An, Cao,XueBing, Xu,Yan, Xia,Yun

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Original abstract

MaoYu Liu, QiWei Peng, Heng Zhai, Yi Wu, ZhuoRan Ma, ZhiCheng Tang, Haoxuan Ouyang, An Chang, XueBing Cao, Yan Xu, Yun Xia Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Yan Xu, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, People’s Republic of China, Email xuyanwxf@126.com Yun Xia, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, 430022, Hubei, People’s Republic of China, Email xiayun19931993@163.comAbstract: 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.Keywords: nanomedicine, drug delivery system, organelle targeting, Parkinson’s disease