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Visualizing Viscosity Changes in Tumor and Rheumatoid Arthritis with a Dual-Targeted NIR Fluorescent Probe
Peng Lei1, Pengjia Wei1, Chuan Dong1
1College of Chemistry and Chemical Engineering & Institute of Environmental Science, Shanxi University, Taiyuan 030006, China.
Abstract:
Targeting mitochondria and nucleus fluorescent probes have emerged as powerful tools for monitoring cellular processes, such as apoptosis and ferroptosis. Nevertheless, only a few near-infrared (NIR) fluorescent probes have been developed for the simultaneous detection of both viscosity and DNA/RNA. Therefore, a mitochondrion- and nucleus-targeted NIR fluorescence probe (BHD) for the detection of viscosity and DNA/RNA was designed and synthesized through the condensation reaction of 1,1,2,3-Tetramethyl-1H-benzo[e]indolium hexafluorophosphate and 4-(dimethylamino)cinnamaldehyde. BHD exhibited remarkable stability under physiological pH and in the presence of biological ions. Due to its cationic structure and strong DNA/RNA binding affinity, BHD was capable of simultaneously targeting both mitochondria and the nucleus. Cellular imaging analysis showed that BHD can effectively detect apoptosis induced by hydrogen peroxide (H2O2) and cisplatin. Interestingly, BHD also revealed that the living cells treated with rotenone for a short duration did not undergo an apoptosis process. By monitoring the variation in fluorescence intensity, BHD can efficiently monitor ferroptosis induced by erastin and further showed that Ferrostatin-1 (Fer-1) was able to inhibit this process. Notably, in vivo imaging of viscosity fluctuations associated with tumoral ferroptosis and rheumatoid arthritis (RA) models has been successfully accomplished.
Insights
A new near-infrared (NIR) fluorescent probe, BHD, simultaneously detects viscosity and DNA/RNA in mitochondria and the nucleus. This probe enables real-time monitoring of cellular processes like apoptosis and ferroptosis in vitro and in vivo.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Cell Biology
Background:
- Fluorescent probes targeting mitochondria and the nucleus are crucial for studying cellular processes like apoptosis and ferroptosis.
- Limited availability of near-infrared (NIR) fluorescent probes for simultaneous detection of viscosity and DNA/RNA hinders cellular research.
- Developing novel probes is essential for advancing our understanding of cellular dynamics and disease mechanisms.
Purpose of the Study:
- To design and synthesize a novel mitochondrion- and nucleus-targeted NIR fluorescent probe (BHD).
- To evaluate the probe's capability for simultaneous detection of viscosity and DNA/RNA.
- To demonstrate the probe's utility in monitoring cellular processes including apoptosis and ferroptosis in vitro and in vivo.
Main Methods:
- Synthesis of the BHD probe via condensation reaction.
- Assessment of BHD stability under physiological conditions.
- Cellular imaging to detect apoptosis induced by H2O2 and cisplatin.
- Monitoring ferroptosis induced by erastin and its inhibition by Ferrostatin-1.
- In vivo imaging of viscosity fluctuations in tumoral ferroptosis and rheumatoid arthritis models.
Main Results:
- BHD demonstrated effective simultaneous targeting of mitochondria and the nucleus due to its cationic structure and DNA/RNA binding affinity.
- BHD successfully visualized apoptosis induced by H2O2 and cisplatin, and importantly, showed rotenone did not induce apoptosis in short durations.
- BHD efficiently monitored erastin-induced ferroptosis and its inhibition by Ferrostatin-1.
- In vivo imaging successfully captured viscosity changes in tumoral ferroptosis and rheumatoid arthritis models.
Conclusions:
- The developed BHD probe is a stable and effective tool for simultaneous detection of viscosity and DNA/RNA in both mitochondria and the nucleus.
- BHD facilitates real-time monitoring of critical cellular events like apoptosis and ferroptosis.
- The probe shows significant potential for in vitro and in vivo biomedical imaging applications, particularly in disease modeling and diagnosis.
