细胞衰老是衰老和年龄相关疾病（ARD）的重要危险因素。经典的 senolytics 达沙替尼和槲皮素 (DQ) 在清除衰老细胞 (SnC) 方面表现出了良好的前景；然而，缺乏选择性对实现最佳结果构成了挑战。尽管最近出现了基于纳米材料的针对 SnC 的方法，但有限的治疗效果和潜在的毒性仍然是一个主要问题。在此，我们开发了一种“双锁状”纳米平台，集成了半乳聚糖涂层和介孔聚多巴胺来包裹抗衰老药物 DQ。这样，DQ仅在β-半乳糖苷酶（β-gal）水平较高和PH值较低的SnCs中释放。此外，纳米颗粒还配备了 2,2,6,6-四甲基哌啶-1-氧基 (Tempo)，以获得增强的光热转换潜力。因此，合成的纳米senolytics在根除SnCs方面表现出显着的特异性和功效，从而在不影响正常组织的情况下逆转小鼠的肺纤维化。在暴露于近红外（NIR）光后，纳米粒子被证明可以有效去除化疗诱导的衰老肿瘤细胞，从而阻碍乳腺癌的生长和转移。总的来说，本研究开发了一种响应 SnC 的“开/关”可切换纳米平台，并产生了一种更安全、有效和可行的方法来延缓衰老或减轻与年龄相关的疾病。本文受版权保护。保留所有权利。本文受版权保护。版权所有。

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 the nanomaterial-based approaches targeting SnCs, limited therapeutic effects and potential toxicity still remain a major concern. Herein, we developed a "double locks-like" nanoplatform that integrated Galactan coating and mesoporous polydopamine to encase the senolytic drug DQ. By this way, DQ was only released in SnCs that were featured with higher levels of β-galactosidase (β-gal) and low PH. Additionally, the nanoparticles were equipped with 2,2,6,6-Tetramethylpiperidine-1-oxyl (Tempo) to gain enhanced photothermal converting potential. Consequently, the synthesized nanosenolytics demonstrated remarkable specificity and efficacy in eradicating SnCs, and accordingly reversed pulmonary fibrosis in mice without affecting normal tissues. Upon exposure of near-infrared (NIR) light, the nanoparticles demonstrated 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. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.