In vivo senescence imaging nanoprobe targets the associated reactive oxygen species
Seung Koo Lee1, Myung Shin Han1, Ching-Hsuan Tung1
1Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, 413 East 69th Street, Box 290, New York, NY 10021, USA. sel2013@med.cornell.edu.
Abstract:
Cellular senescence, a cell-cycle arrest state upon stress or damage, can adversely impact aging and cancers. We have designed a novel near infrared fluorogenic nanoprobe, named D3, which can only be turned on by highly elevated levels of reactive oxygen species (ROS), critical players for the induction and maintenance of senescence, for real-time senescence sensing and imaging. In contrast to glowing senescent cells, non-senescent cells whose ROS levels are too low to activate the D3 signal remain optically silent. Upon systemic injection into senescent tumor-bearing mice, the D3 nanoprobe quickly accumulates in tumors, and its fluorescence signal is turned on specifically by senescence-associated ROS in the senescent tumors. The fluorescence signal at senescent tumors was 3-fold higher than that of non-senescent tumors. This groundbreaking design introduces a novel activation mechanism and a powerful imaging nanoprobe to identify and assess cellular senescence in living organisms.
Insights
Researchers developed a novel near-infrared nanoprobe, D3, for real-time imaging of cellular senescence. This probe specifically detects senescence-associated reactive oxygen species (ROS) in tumors, offering a new tool for aging and cancer research.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Cell Biology
Background:
- Cellular senescence is a state of irreversible cell-cycle arrest implicated in aging and cancer.
- Reactive oxygen species (ROS) play a critical role in the induction and maintenance of senescence.
- Current methods for detecting senescence in vivo are limited.
Purpose of the Study:
- To design and validate a novel near-infrared fluorogenic nanoprobe (D3) for real-time imaging of cellular senescence.
- To investigate the specificity of D3 for senescence-associated ROS.
- To assess the utility of D3 for imaging senescent tumors in vivo.
Main Methods:
- Design and synthesis of the D3 nanoprobe, a near-infrared fluorogenic probe activated by high ROS levels.
- In vitro validation of D3's activation mechanism by ROS.
- Systemic injection of D3 into senescent tumor-bearing mice for in vivo imaging.
- Quantification of fluorescence signal in senescent versus non-senescent tumors.
Main Results:
- The D3 nanoprobe exhibits fluorescence only in the presence of highly elevated ROS levels, characteristic of senescent cells.
- D3 specifically accumulates in senescent tumors after systemic administration.
- Fluorescence signal intensity in senescent tumors was 3-fold higher than in non-senescent tumors.
- Non-senescent cells remained optically silent due to low ROS levels.
Conclusions:
- The D3 nanoprobe represents a novel and powerful tool for non-invasive, real-time imaging and assessment of cellular senescence in living organisms.
- This technology has significant potential for advancing research in aging and cancer by enabling precise identification of senescent cells and tumors.
- The unique activation mechanism of D3 provides a new strategy for developing targeted molecular imaging agents.
More Related Videos
Related Concept Videos
Mitochondria
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Oxidation and Reduction of Organic Molecules
The removal of an electron from a molecule, results in a...
Electron Transport Chain: Complex III and IV
The Effect of Aging on Tissues
Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...


