Nature communicationsDec 13, 2025

Nanoparticle system that activates iron-dependent cell death to remove aging cells in age-related diseases

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A senescent-cell-responsive nanoplatform eliminated senescent cells and improved physical fitness measures in aged mice.

Evidence

A preclinical nanoplatform study tested HK-PCGC, combining β-galactosidase activation, Ce6-mediated reactive oxygen species generation, ferritin targeting, and ferroptosis induction in senescent cells and aged mice.

Caveat

The approach is supported by cellular and aged-mouse evidence, not human aging or age-associated disease outcomes.

Simplified

Accumulation of senescent cells is associated with aging and age-related diseases. However, current clearance therapies targeting senescent cells are often limited by low efficiency, poor specificity, and insufficient penetration. Here we develop a nano-platform composed of a probe (GD) that can be specifically activated by senescent cells, a photosensitizer (Ce6), and a peptide (HK) for targeting ferritin, named HK-PCGC. We show that upon entering senescent cells, GD is activated by high levels of β-galactosidase, releasing fluorescence to excite Ce6. Ce6 then generates reactive oxygen species to eliminate these cells. Additionally, we find that under the guidance of the peptide HK, our system degrades ferritin to trigger ferroptosis, further eliminating senescent cells. Collectively, we demonstrate that HK-PCGC can effectively eliminate senescent cells, reduce the senescence-associated secretory phenotype, and safely improve the physical fitness of aged mice. This study integrates senescent cell responsiveness, laser-free photodynamic therapy, and induction of ferroptosis, offering a potential approach for delaying aging.