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Targeted Supramolecular Senolytics by Enzyme-Responsive Disassembly and Intracellular Polymerization
Sangpil Kim1, Jaeeun Lee1, Yumi Cho2
1Department of Chemistry, UNIST, Ulsan 44919 (Republic of Korea).
ACS Applied Materials & Interfaces
|January 12, 2026
Summary
Researchers developed a novel self-assembly system that selectively targets senescent cells. This system responds to elevated reactive oxygen species (ROS) and alkaline phosphatase (ALP) activity, offering a new therapeutic strategy for age-related diseases.
Area of Science:
- Biomaterials Science
- Cell Biology
- Nanomedicine
Background:
- Senescent cell elimination shows therapeutic potential for age-related diseases.
- Selective targeting of senescent cells remains a significant challenge in therapeutic development.
Purpose of the Study:
- To develop a dual-responsive self-assembly system for selective senescent cell targeting.
- To engineer a system responding to reactive oxygen species (ROS) and alkaline phosphatase (ALP) activity.
Main Methods:
- Designed a monomer (p-Mito-1) with phosphate-protected thiol groups and mitochondrial-targeting moieties.
- Engineered zwitterionic nanostructures that disassemble in senescent cells.
- Investigated ROS-induced transformation into bioactive fibers and apoptosis induction.
Main Results:
- p-Mito-1 selectively targeted senescent RPE cells (IC50 ≈ 80 μM) with minimal toxicity to normal RPE cells.
- The system demonstrated efficacy in an AMD-relevant model, depleting senescent RPE cells.
- Validated the dual-responsive system's potential for precise senescent cell targeting.
Conclusions:
- Dual-responsive supramolecular systems offer a precise strategy for targeting senescent cells.
- This modular design approach holds promise for interventions in aging-related diseases.
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