A versatile drug delivery system targeting senescent cells

被引：226

作者：

Munoz-Espin, Daniel ^{[1
,2
]}

Rovira, Miguel ^{[1
,3
]}

Galiana, Irene ^{[4
,5
]}

Gimenez, Cristina ^{[4
]}

Lozano-Torres, Beatriz ^{[4
,5
]}

Paez-Ribes, Marta ^{[2
]}

Llanos, Susana ^{[1
]}

Chaib, Selim ^{[1
,3
]}

Munoz-Martin, Maribel ^{[1
,3
]}

Ucero, Alvaro C. ^{[6
]}

Garaulet, Guillermo ^{[7
]}

Mulero, Francisca ^{[7
]}

Dann, Stephen G. ^{[8
]}

VanArsdale, Todd ^{[8
]}

Shields, David J. ^{[8
]}

Bernardos, Andrea ^{[4
,5
]}

Murguia, Jose Ramon ^{[4
,5
]}

Martinez-Manez, Ramon ^{[4
,5
,9
]}

Serrano, Manuel ^{[1
,3
,10
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Tumor Suppress Grp, Madrid, Spain

[2] Univ Cambridge, CRUK Cambridge Ctr, Early Detect Programme, Dept Oncol,Hutchison MRC Res Ctr, Cambridge, England

[3] Barcelona Inst Sci & Technol BIST, Cellular Plast & Dis Grp, Inst Res Biomed IRB Barcelona, Barcelona, Spain

[4] Univ Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr, Univ Politecn Valencia, Valencia, Spain

[5] CIBER BBN, Madrid, Spain

[6] Spanish Natl Canc Res Ctr CNIO, Genes Dev & Dis Grp, Madrid, Spain

[7] Spanish Natl Canc Res Ctr CNIO, Mol Imaging Unit, Madrid, Spain

[8] Pfizer Inc, Oncol R&D Grp, Pfizer Worldwide Res & Dev, La Jolla, CA USA

[9] Univ Politecn Valencia, Dept Quim, Valencia, Spain

[10] Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain

来源：

EMBO MOLECULAR MEDICINE | 2018年 / 10卷 / 09期

基金：

欧洲研究理事会;

关键词：

chemotherapy; fibrosis; nanomedicine; palbociclib; senescence; MESOPOROUS SILICA NANOPARTICLES; CELLULAR SENESCENCE; SECRETORY PHENOTYPE; BETA-GALACTOSIDASE; OXIDATIVE STRESS; DOXORUBICIN; INHIBITION; APOPTOSIS; GENE; CONTRIBUTES;

D O I：

10.15252/emmm.201809355

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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 beta-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.

引用

页数：18

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