ROS-Targeted Nanoprobes for Detection and Imaging of Cellular Senescence

Background & Unmet Need

• Cellular senescence is a state of irreversible cell cycle arrest associated with aging, in which cells stop proliferating
• Senescent cells are drug resistant and may secrete factors such as cytokines into surrounding tissues, causing low-grade inflammation
• Senescence can be caused by cellular stress or damage, including mitochondrial dysfunction, oxidative stress, or DNA damage
• Cells can also become senescent in response to chemotherapy and escape treatment, leading to future tumor recurrence
• Senescence is currently imaged using beta-galactosidase (Xgal); however, this label is not senescence-specific and requires cell fixing and long incubation times
• Unmet Need: Improved methods for detection and imaging of senescent cells

Technology Overview

• The Technology: A novel fluorogenic nanoprobe for labeling cellular senescence via detection of reactive oxygen species (ROS)
• ROS are known to play a role in progression and maintenance of cell senescence, and ROS levels are directly related to induction of cellular senescence
• The inventors have created a novel nanoprobe, D3, which fluoresces in response to high levels of ROS, thereby labeling senescent cells
• PoC Data: In tumor-bearing mice, D3 accumulated quickly and preferentially in tumors when administered intravenously
• Fluorescent signal from D3 was specifically turned on in senescent tumors, which were induced via treatment of tumor-bearing mice with Palbociclib
• The fluorescence signal from D3 in senescent tumors was 3-fold higher than that of non-senescent tumors

Technology Applications

• Imaging nanoprobe to identify senescent tumors following chemotherapy
• Long-term study of disease progression and treatment response for senescence-associated conditions, including aging and fibrosis
• Real-time imaging of changes in cellular senescence
• Identification and isolation of senescent cells for further research

Technology Advantages

• D3 is remarkably stable in normal physiological conditions
• D3 does not require cells to be fixed or to undergo long incubation times
• Fluorescence intensity of D3 is dependent on ROS production level and corresponds to senescence progression, allowing for real-time imaging

Figure 1: D3 detects palbociclib-induced senescence in vitro