Abstract:
:Senescent 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.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Muñoz-Espín D,Rovira M,Galiana I,Giménez C,Lozano-Torres B,Paez-Ribes M,Llanos S,Chaib S,Muñoz-Martín M,Ucero AC,Garaulet G,Mulero F,Dann SG,VanArsdale T,Shields DJ,Bernardos A,Murguía JR,Martínez-Máñez R,Serrano Mdoi
10.15252/emmm.201809355subject
Has Abstractpub_date
2018-09-01 00:00:00issue
9eissn
1757-4676issn
1757-4684pii
emmm.201809355journal_volume
10pub_type
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