Cellular senescence has recently been recognized as one of the hallmarks of cancer, aging, as well as many age‐related disorders, sparking significant interest in the development of senolytics, compounds that can remove senescent cells. However, most current pharmacological strategies face challenges related to non‐specific delivery, leading to significant side effects that hinder safe and effective treatments. To address these issues, galactose‐functionalized amphiphiles are synthesized that can self‐assemble into micelles and be loaded with a senolytic cargo. These galactose‐micelles are responsive to the lysosomal β‐galactosidase enzyme, present in elevated amounts in senescent cells, and are employed for specific delivery of the senolytic Bcl2‐inhibitor Navitoclax. This novel formulation showed reduced delivery and toxicity to non‐senescent cells, thereby increasing the senolytic index of Navitoclax and making it suitable for future in vivo experimental designs to improve selectivity and safety profiles.

中文翻译：

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提高衰老细胞特异性、半乳糖功能化胶束纳米载体的治疗效果


细胞衰老最近被认为是癌症、衰老以及许多与年龄相关的疾病的标志之一，引发了人们对 senolytics（可以去除衰老细胞的化合物）开发的浓厚兴趣。然而，目前的大多数药理学策略都面临着与非特异性递送相关的挑战，导致严重的副作用，阻碍了安全有效的治疗。为了解决这些问题，合成了半乳糖官能化的两亲物，它们可以自组装成胶束并装载 senolytic 货物。这些半乳糖胶束对溶酶体 β-半乳糖苷酶有反应，溶酶体 -半乳糖苷酶在衰老细胞中的含量很高，并用于特异性递送 senolytic Bcl2 抑制剂 Navitoclax。这种新型制剂显示出对非衰老细胞的递送和毒性降低，从而提高了 Navitoclax 的 senolytic 指数，并使其适用于未来的体内实验设计，以提高选择性和安全性。