Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6559
A versatile drug delivery system targeting senescent cells
Muñoz Espin, Daniel CNIO | Rovira, Miguel CNIO | Galiana, Irene | Giménez, Cristina | Lozano-Torres, Beatriz | Paez-Ribes, Marta | Llanos, Susana CNIO | Chaib, Selim | Muñoz-Martín, Maribel | Ucero, Alvaro C | Garaulet, Guillermo | Mulero, Francisca CNIO | Dann, Stephen G | VanArsdale, Todd | Shields, David J | Bernardos, Andrea | Murguía, José Ramón | Martínez-Máñez, Ramón | Serrano Marugan , Manuel CNIO
EMBO Mol Med. 2018; 10 (9): pii: e9355.
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.
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