A versatile drug delivery system targeting senescent cells.
Dann, Stephen G
Shields, David J
Murguía, José Ramón
EMBO molecular medicine
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Muñoz-Espín, D., Rovira, M., Galiana, I., Giménez, C., Lozano-Torres, B., Paez-Ribes, M., Llanos, S., et al. (2018). A versatile drug delivery system targeting senescent cells.. EMBO molecular medicine, 10 (9)https://doi.org/10.15252/emmm.201809355
Senescent cells accumulate in multiple ageing-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 targeted 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.
Lysosomes, Animals, Mice, Neoplasms, Disease Models, Animal, Piperazines, Pyridines, beta-Galactosidase, Galactose, Oligosaccharides, Cytotoxins, Fluorescent Dyes, Drug Delivery Systems, Staining and Labeling, Neoplasm Transplantation, Drug Compounding, Cell Survival, Heterografts, Cellular Senescence
Cancer Research UK (C96/A25177)
External DOI: https://doi.org/10.15252/emmm.201809355
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280524
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/