A versatile drug delivery system targeting senescent cells

Senescent cells accumulate in many ageing-associated diseases such as pulmonary fibrosis, and targeting these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high ß-galactosidase activity of senescent cells to design a targeted drug delivery system based on the encapsulation of drugs with galacto-oligosaccharides (GalNP beads). In this experiment we show that gal-encapsulated rhodamine target senescent cells in the context of pulmonary fibrosis in mice. Overall design: 8- to 10-week-old C57BL/6 wild-type mice were intratracheally inoculated with bleomycin at 1.5 U/kg of body weight. Two weeks later mice were i.v. injected with 200 µl of a solution of GalNP beads loaded with rhodamine [GalNP(rho)] at 4 mg/ml, equivalent to 1 mg/kg of deliverable rhodamine. 6 hours later mice were sacrificed and lung cells were analysed by flow cytometry and sorted into Rho+ or Rho- cells, all CD45-CD31-.

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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 M