Authors
Ke Li, Zeqing Li, Yuan Xue, Hao Liu, Jiangrong Guo, Xuemei Zhang, Bin Li, Yongjun Rui
Published in
Materials today. Bio. Volume 41. Pages 103751. Epub Oct 12, 2026.
Abstract
The senescence of leptin receptor-positive (LepR+) cells in bone marrow contributes to the development of the aged bone marrow microenvironment, and rescuing LepR+ cell senescence holds promise for alleviating age-related osteoporosis. This study reveals that senescent LepR+ cells establish a pro-senescent vicious cycle driven by decreased NO, reduced Mg2+, and continuously accumulated reactive oxygen species (ROS). To break this cycle, we constructed an aged microenvironment-triggered nanoreactor capable of releasing NO/Mg2+ and scavenging ROS to reverse cellular senescence. In this system, the nanoreactor (LPM) was fabricated via a thin-film hydration method, in which L-arginine was loaded into methoxy poly(ethylene glycol)-block-poly(propylene sulfide) (mPEG-b-PPS) and stabilized by Mg2+-mediated crosslinking. Coating LPM with senescent LepR+ cell membranes generated CLPM, which exhibited superior targeting to LepR+ cells, efficient NO/Mg2+ release, and potent ROS scavenging activity. CLPM treatment effectively rejuvenated senescent LepR+ cells, as evidenced by reduced senescence phenotypes and enhanced bone marrow regeneration. RNA sequencing further confirmed that CLPM disrupted the vicious cycle in senescent LepR+ cells and remodeled the aged bone marrow. Collectively, our findings suggest that the CLPM nanoreactor offers a promising approach for rejuvenation of the aging skeletal system.
PMID:
42927243
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.
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