In vivo targeted-imaging of mitochondrial acidification in an aristolochic acid I-induced nephrotoxicity mouse model by a fluorescent/photoacoustic bimodal probe

• Published in: Materials today bio 2024-10, Vol.28, p.101240, Article 101240
• Main Authors: Xu, Li, Chen, Li, Liu, Hongwen, Chen, Xingwang, Zhang, Shenghang
• Format: Article
• Language: English
• Subjects: Aristolochic acid; Fluorescent imaging; Full Length; In vivo mitophagy; Nephrotoxicity; Photoacoustic imaging
• ISSN: 2590-0064; 2590-0064
• DOI: 10.1016/j.mtbio.2024.101240

Aristolochic acid I (AAI), a natural compound in aristolochia type Chinese medicinal herb, is generally acknowledged to have nephrotoxicity, which may be associated with mitophagy. Mitophagy is a cellular process with important functions that drive AAI-induced renal injury. Mitochondrial pH is currently measured by fluorescent probes in cell culture, but existing probes do not allow for in situ imaging of AAI-induced mitophagy in vivo. We developed a ratiometric fluorescent/PA dual-modal probe with a silicon rhodamine fluorophore and a pH-sensitive hemicyanine dye covalently linked via a short chain to obtain a FRET type probe. The probe was used to measure AAI-mediated mitochondrial acidification in live cells and in vivo. The Förster resonance energy transfer (FRET)-mediated ratiometric and bimodal method can efficiently eliminate signal variability associated with the commonly used one-emission and single detection mode by ratiometric two channels of the donor and acceptor. The probe has good water-solubility and low molecular weight with two positively charged, facilitating its precise targeting into renal mitochondria, where the fluorescent/PA changes in response to mitochondrial acidification, enabling dynamic and semi-quantitative mapping of subtle changes in mitochondrial pH in AAI-induced nephrotoxicity mouse model for the first time. Also, the joint use of L-carnitine could mitigate the mitophagy in AAI-induced nephrotoxicity. Entry for the Table of Contents. A kidney and mitochondria dual targeted, pH response molecule probe with ratiometric near-infrared fluorescent/PA signal was developed for in situ and dual channel and dual modal imaging of mitophagy in AAI induced renal injury. [Display omitted] •In situ visualization of AAI-induced nephrotoxicity was achieved by fluorescent/PA dual modal imaging.•Engineering of a FRET-mediated ratiometric probe enables mapping of subtle changes in mitochondrial pH.•In vivo targeted-imaging of AAI -induced nephrotoxicity was achieved for the first time.•The joint use of AAI and L-carnitine could mitigate the mitophagy in AAI-induced kidney injury.