Senolytic Therapy Enabled by Senescent Cell-Sensitive Biomimetic Melanin Nano-Senolytics.

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.