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.

Nanoscale
|December 22, 2023
PubMed

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.

Related Concept Videos

Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Oxidation and Reduction of Organic Molecules01:19

Oxidation and Reduction of Organic Molecules

Energy production within a cell involves many coordinated chemical pathways. Most of these pathways are combinations of oxidation and reduction reactions, which occur at the same time. An oxidation reaction strips an electron from an atom in a compound, and the addition of this electron to another compound is a reduction reaction. Because oxidation and reduction usually occur together, these pairs of reactions are called redox reactions.
The removal of an electron from a molecule, results in a...
Electron Transport Chain: Complex III and IV01:43

Electron Transport Chain: Complex III and IV

During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
The Effect of Aging on Tissues01:19

The Effect of Aging on Tissues

Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
Aging01:26

Aging

Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in 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...