Development and Application of a BODIPY Carbazole Derivative Probe for Lysosomal Imaging: Insights into Lysosomal Dynamics and Dysfunction in Inflammation-Related Diseases.

ACS Appl Mater Interfaces

Department of Medical Ultrasound, State Key Laboratory of Biotherapy, Huaxi MR Research Center (HMRRC), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital of Sichuan University, Sichuan University, Chengdu 610000, Sichuan, People's Republic of China.

Published: December 2024

Inflammation is crucial in neurodegenerative and chronic diseases, including Alzheimer disease (AD) and liver fibrosis. To gain a deeper understanding of lysosomal functions in cellular physiology and disease mechanisms, we developed a carbazole-based BODIPY lysosomal probe, designated LysoI. This probe specifically targets lysosomes within 15 min and exhibits a Stokes shift of approximately 180 nm, enabling continuous incubation for up to 5 h without the need for washing steps. Interestingly, LysoI remained effective for long-term imaging, even up to 24 h poststaining. Despite varying pH values and conditions, such as autophagy, apoptosis, and inflammation, it consistently provides excellent lysosomal imaging. Notably, inflammation disrupts lysosomal morphology and motility, as evidenced by an increased size, a decrease in number, and a reduction in movement speed, as observed with LysoI. Furthermore, lysosomal rupture and impaired clearance may exacerbate inflammation and contribute to cellular apoptosis. These findings suggest that lysosomal dysfunction is closely associated with disease progression; therefore, protection and repair targeting lysosomes may offer promising strategies for treating inflammation-related diseases.

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http://dx.doi.org/10.1021/acsami.4c17607DOI Listing

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