Improved Therapeutic Efficiency of Senescent Cell‐specific, Galactose‐Functionalized Micelle Nanocarriers

Abstract 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.