Senolytic Therapy Enabled by Senescent Cell-Sensitive Biomimetic Melanin Nano-Senolytics.
Adv Healthc Mater
; 13(23): e2401085, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-38796738
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 ß-galactosidase (ß-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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Senescencia Celular
/
Nanopartículas
/
Senoterapéuticos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Adv Healthc Mater
Año:
2024
Tipo del documento:
Article
País de afiliación:
China