Materials today. BioOct 25, 2026

Nanoparticles that renew aged LepR+ cells to improve old bone marrow

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 26, 2026

Abstract

Senescent leptin receptor-positive (LepR⁺) cells contribute to age-related osteoporosis by establishing a pro-senescent cycle characterized by decreased nitric oxide (NO), reduced magnesium (Mg²⁺), and increased reactive oxygen species (ROS).

The senescence of LepR⁺ cells in bone marrow may lead to a deteriorating microenvironment associated with aging.
A newly developed nanoreactor (CLPM) effectively targets LepR⁺ cells, releasing NO and Mg²⁺ while scavenging ROS.
Treatment with CLPM rejuvenates senescent LepR⁺ cells, reducing senescence markers and enhancing bone marrow regeneration.
RNA sequencing indicates that CLPM disrupts the vicious cycle in senescent LepR⁺ cells and alters the aged bone marrow environment.

Simplified

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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Nanoparticles that renew aged LepR+ cells to improve old bone marrow

Abstract

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