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Updated: Jun 25, 2025
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Senolytic Therapy Enabled by Senescent Cell-Sensitive Biomimetic Melanin Nano-Senolytics
Hairui Zhang1,2, Xiaoling Xu1,3, Xin Shou1
1Key Laboratory of Artificial Organs and Computational Medicine, Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, Zhejiang, 310015, China.
Abstract:
Cellular senescence is a significant risk factor for aging and age-related diseases (ARD). The canonical senolytics Dasatinib and Quercetin (DQ) have shown promise in clearing senescent cells (SnCs); however, the lack of selectivity poses a challenge in achieving optimal outcomes. Despite the recent occurrence of nanomaterial-based approaches targeting SnCs, limited therapeutic effects, and potential toxicity still remain a major concern. Herein, a "double locks-like" nanoplatform is developed that integrated Galactan coating and mesoporous polydopamine to encase the senolytic drug DQ. By this way, DQ is only released in SnCs that are featured with higher levels of β-galactosidase (β-gal) and low PH. Additionally, the nanoparticles are equipped with 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) to gain enhanced photothermal converting potential. Consequently, the synthesized nanosenolytics demonstrate remarkable specificity and efficacy in eradicating SnCs, and accordingly reverse pulmonary fibrosis in mice without affecting normal tissues. Upon exposure of near-infrared (NIR) light, the nanoparticles demonstrate to efficiently remove senescent tumor cells inducted by chemotherapy, thereby hindering the outgrowth and metastasis or breast cancer. Collectively, the present study develops an "On/Off" switchable nanoplatform in response to SnCs, and produces a more safe, efficient, and feasible way to delay aging or alleviate age-associated diseases.
Insights
This study introduces a novel nanoplatform that selectively targets and eliminates senescent cells (SnCs) using the senolytic drug Dasatinib and Quercetin (DQ). This targeted approach offers a safer and more effective method for treating age-related diseases and potentially delaying aging.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Gerontology
- Pharmacology
Background:
- Cellular senescence is a key risk factor for aging and age-related diseases (ARD).
- Existing senolytics like Dasatinib and Quercetin (DQ) lack selectivity, limiting their therapeutic potential.
- Nanomaterial-based approaches for senescent cell targeting face challenges in efficacy and toxicity.
Purpose of the Study:
- To develop a "double locks-like" nanoplatform for selective delivery of senolytics to senescent cells (SnCs).
- To enhance the therapeutic efficacy and safety of senolytic treatment for aging and related diseases.
- To create an "On/Off" switchable nanoplatform responsive to the senescent cell microenvironment.
Main Methods:
- Encapsulation of Dasatinib and Quercetin (DQ) within a nanoplatform featuring Galactan coating and mesoporous polydopamine.
- Integration of 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) for enhanced photothermal conversion.
- Utilizing senescent cell-specific markers (high β-galactosidase, low pH) for drug release and near-infrared (NIR) light for activation.
Main Results:
- The nanosenolytics demonstrated high specificity and efficacy in eradicating senescent cells (SnCs).
- Pulmonary fibrosis in mice was reversed without affecting normal tissues.
- Senescent tumor cells induced by chemotherapy were efficiently removed upon NIR light exposure, inhibiting tumor growth and metastasis.
Conclusions:
- The developed nanoplatform provides a safe, efficient, and feasible method for targeting senescent cells (SnCs).
- This "On/Off" switchable nanoplatform holds promise for delaying aging and alleviating age-associated diseases (ARD).
- The targeted delivery system enhances senolytic therapy outcomes, overcoming limitations of conventional approaches.
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