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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).

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|January 12, 2026
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Summary
This summary is machine-generated.

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.

Keywords:
alkaline phosphatasedisulfide bondintracellular polymerizationmitochondriasenolytics

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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.