Muñoz Espin, DanielRovira, MiguelGaliana, IreneGiménez, CristinaLozano-Torres, BeatrizPaez-Ribes, MartaLlanos, SusanaChaib, SelimMuñoz-Martín, MaribelUcero, Alvaro CGaraulet, GuillermoMulero, FranciscaDann, Stephen GVanArsdale, ToddShields, David JBernardos, AndreaMurguía, José RamónMartínez-Máñez, RamónSerrano Marugan , Manuel2018-11-022018-11-022018-09EMBO Mol Med. 2018; 10 (9): pii: e9355.1757-4676http://hdl.handle.net/20.500.12105/6559Senescent cells accumulate in multiple aging-associated diseases, and eliminating these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high lysosomal β-galactosidase activity of senescent cells to design a drug delivery system based on the encapsulation of drugs with galacto-oligosaccharides. We show that gal-encapsulated fluorophores are preferentially released within senescent cells in mice. In a model of chemotherapy-induced senescence, gal-encapsulated cytotoxic drugs target senescent tumor cells and improve tumor xenograft regression in combination with palbociclib. Moreover, in a model of pulmonary fibrosis in mice, gal-encapsulated cytotoxics target senescent cells, reducing collagen deposition and restoring pulmonary function. Finally, gal-encapsulation reduces the toxic side effects of the cytotoxic drugs. Drug delivery into senescent cells opens new diagnostic and therapeutic applications for senescence-associated disorders.engVoRhttp://creativecommons.org/licenses/by/4.0/ChemotherapyFibrosisNanomedicinePalbociclibSenescenceAtribución 4.0 Internacional30012580109e935510.15252/emmm.2018093551757-4684EMBO molecular medicineopen access