A General Strategy to Fine-Tune Group 14 Rhodamines for Ultrahigh Signal-to-Noise Ratio Labeling In Vivo by Nano-Aggregation

  • Ning Wang
  • , Ting Wang
  • , Mengting Fan
  • , Chen Li
  • , Yue Tian
  • , Xiaoyan Cui*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Ultrahigh signal-to-noise ratio (SNR) labeling enables precise visualization of biological structures in vivo. We boosted fluorogenicity in group-14-rhodamines by comprehensively manipulating their dynamics in physical (aggregate/monomer, KA/M) and chemical (closed/open spirolactone, KC/O) states. Fluorogenic rhodamines were designed by group 14 (C, Si, Ge) substituted bridging regions in xanthene with tuned dialkylation. We quantified the impact of alkylation with the hydrophobicity (logP) over a wide range and confirmed that SNR can be sharply improved, owing to the promoted nano-aggregation (KA/M) with high logP. Integrating KA/M with KC/O mechanisms, unparalleled fluorogenicity was observed in group-14-rhodamines: HaloTag probe with dipentylsilyl exhibits remarkable fluorogenicity (>2000) in vitro, enabling no-wash and multicolor super-resolution stimulated emission depletion imaging of high SNR (>300) in vivo. Overexpression of αvβ3 was sensitively tracked in vivo by RGDyK-based fluorogenic SiR probe through tuned KA/M. Our proposed strategy has significantly promoted the fluorogenicity of group 14 rhodamines as a general mechanism.

Original languageEnglish
Article numbere70077
JournalAggregate
Volume6
Issue number8
DOIs
StatePublished - Aug 2025

Keywords

  • fluorescence imaging
  • nano-aggregates
  • signal-to-noise ratio
  • substituted rhodamine
  • super-resolution microscopy

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