A ratiometric fluorogenic nanoprobe for real-time quantitative monitoring of lysosomal pH

Autor: Caroline Brommesson, Anna du Rietz, Zhangjun Hu, Xin Zhang, Xiongyu Wu, Kajsa Uvdal, Jiwen Hu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Popis: Lysosomes are known as key players in cellular signalling and act as terminal degradation stations involved in a multitude of cellular processes. Being a highly influential physiological factor, pH is essential in the regulation of lysosome-mediated physiological and pathological processes. Aberrant pH fluctuations are highly related to lysosomal dysfunction that correlates to lysosomal storage diseases and neurodegenerative disorders. As such, real-time quantitative monitoring of lysosomal pH (pHL) is crucial for gaining insight into lysosomal dysfunction but challenging by the lack of effective lysosome-specific probes with high signal fidelity. Toward this end, we have proposed a lysosomal fluorogenic nanoprobe (TR-MP) for reliable ratiometric measuring of pHL. It is fabricated by rational manipulation of fluorescence resonance energy transfer (FRET) in a tailorable nanoplatform. The nanoprobe consists of biocompatible silica nanoparticles assembled with a pH-sensitive rhodamine derivative (RDM-TEOS) as an acceptor and aggregation-induced emission (AIE) fluorophore (TPE-OMe) as a donor to ensure high energy transfer efficiency. Further equipped with cell-penetrating facilitator and morpholine to enable effective cell-internalization and high lysosome affinity of TR-MP. Results show that TR-MP can quantitatively measure pH in a range of 3.0 - 7.0 and detect pHL fluctuations in live cells under various stimuli, as well as real-time monitor pHL during apoptosis. Funding Agencies|STINT Joint China-Sweden Mobility Project [CH2017-7243]; Swedish Research Council (VR)Swedish Research Council [VR 2019-02409, 2020-05437]; China Scholarship Council (CSC)China Scholarship Council; Carl Tryggers Stiftelse [CTS 19:379]; Swedish Government strategic faculty grant in material science (SFO, MATLIU) in Advanced Functional Materials (AFM) (VR) [5.1-2015-5959]; Centre in Nano Science and technology at LiTH (CeNano); LiU Cancer network at Linkoping University
Databáze: OpenAIRE