Aged microenvironment-triggered nanoreactors rejuvenate senescent LepR⁺ cells to remodel aged bone marrow.
4 affiliations
- 1Orthopedic Institute (Wuxi Key Laboratory of Orthopaedics & Wuxi Key Laboratory of Sports Medicine), Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214062, PR China.
- 2Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, PR China.
- 3Department of Orthopedic Trauma, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214062, PR China.
- 4Minimally Invasive Orthopedic Institute of Soochow University, Wuxi Ninth People's Hospital Affiliated to Soochow University, Wuxi, 214062, PR China.
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.
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BibTeX
@article{li2026aged,
title = {{Aged microenvironment-triggered nanoreactors rejuvenate senescent LepR⁺ cells to remodel aged bone marrow.}},
author = {Ke Li and Zeqing Li and Yuan Xue and Hao Liu and Jiangrong Guo and Xuemei Zhang and Bin Li and Yongjun Rui},
journal = {Materials today. Bio},
year = {2026},
month = oct,
doi = {10.1016/j.mtbio.2026.103751},
url = {https://europepmc.org/article/MED/42927243},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Aged microenvironment-triggered nanoreactors rejuvenate senescent LepR⁺ cells to remodel aged bone marrow.
AU - Ke Li
AU - Zeqing Li
AU - Yuan Xue
AU - Hao Liu
AU - Jiangrong Guo
AU - Xuemei Zhang
AU - Bin Li
AU - Yongjun Rui
PY - 2026
DA - 2026/10/12
JO - Materials today. Bio
DO - 10.1016/j.mtbio.2026.103751
UR - https://europepmc.org/article/MED/42927243
AB - 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.
SN - 2590-0064
ER -