Open AccessA versatile drug delivery system targeting senescent cells
Author(s) -
MuñozEspín Daniel,
Rovira Miguel,
Galiana Irene,
Giménez Cristina,
LozanoTorres Beatriz,
PaezRibes Marta,
Llanos Susana,
Chaib Selim,
MuñozMartín Maribel,
Ucero Alvaro C,
Garaulet Guillermo,
Mulero Francisca,
Dann Stephen G,
VanArsdale Todd,
Shields David J,
Bernardos Andrea,
Murguía José Ramón,
MartínezMáñez Ramón,
Serrano Manuel
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201809355
Subject(s) - library science , humanities , art , computer science
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.