Multifunctional Nanoprobe for the Delivery of Therapeutic siRNA and Real-Time Molecular Imaging of Parkinson's Disease Biomarkers.

Affiliation

Li R(1), Li Y(2), Mu M(2), Yang B(1), Chen X(1), Lee WYW(3), Ke Y(2), Yung WH(2), Tang BZ(4), Bian L(1)(5).
Author information:
(1)Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, New Territories, 999077 Hong Kong, P. R. China.
(2)School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, 999077 Hong Kong, P. R. China.
(3)Department of Orthopedic and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, 999077 Hong Kong, P. R. China.
(4)Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, 999077 Hong Kong, P. R. China.
(5)The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen 518000, China.

Abstract

Parkinson's disease (PD) has been recently associated with the excessive expression of matrix metalloproteinase 3 (MMP3). One of the major challenges in treating PD is to effectively detect and inhibit the early MMP3 activities to relieve the neural stress and inflammation responses. Previously, numerous upconversion nanoparticle (UCNP)-based nanoprobes have been designed for the detection of biomarkers in neurodegenerative diseases. To further improve the performance of the conventional nanoprobes, we introduced novel reporting units and integrated the therapeutic reagents to fabricate a theragnostic platform for PD and other neurodegenerative diseases. Here, we designed a multifunctional UCNP/aggregation-induced emission luminogen (AIEgen)-based nanoprobe to effectively detect the time-lapse MMP3 activities in the inflammatory catecholaminergic SH-SY5Y cells and simultaneously deliver the MMP3-siRNA into the stressed catecholaminergic SH-SY5Y cells, inhibiting the MMP3-induced inflammatory neural responses. The unique features of our UCNP/AIEgen-based nanoprobe platform shed light on the development of a novel theragnostic probe for the early diagnosis and cure of neurodegenerative diseases.