- -

A versatile drug delivery system targeting senescent cells

RiuNet: Repositorio Institucional de la Universidad Politécnica de Valencia

Compartir/Enviar a

Citas

Estadísticas

  • Estadisticas de Uso

A versatile drug delivery system targeting senescent cells

Mostrar el registro sencillo del ítem

Ficheros en el ítem

Thumbnail
Nombre: Muñoz-Espín;Rovir ...
Tamaño: 2.239Mb
Formato: PDF
Descripción: Versión editorial
Abrir
dc.contributor.author Muñoz-Espín, Daniel es_ES
dc.contributor.author Rovira, M. es_ES
dc.contributor.author Galiana, Irene es_ES
dc.contributor.author Giménez Morales, Cristina es_ES
dc.contributor.author Lozano-Torres, Beatriz es_ES
dc.contributor.author Páez Ribes, M. es_ES
dc.contributor.author LLanos, Susana es_ES
dc.contributor.author Chaib, Selim es_ES
dc.contributor.author Muñoz-Martín, M. es_ES
dc.contributor.author Ucero, Alvaro C. es_ES
dc.contributor.author Garaulet, G. es_ES
dc.contributor.author Mulero, F. es_ES
dc.contributor.author Dann, S.G. es_ES
dc.contributor.author VanArsdale, T. es_ES
dc.contributor.author Shields, D.J. es_ES
dc.contributor.author Bernardos Bau, Andrea es_ES
dc.contributor.author Murguía, Jose R. es_ES
dc.contributor.author Martínez-Máñez, Ramón es_ES
dc.date.accessioned 2020-05-15T03:03:20Z
dc.date.available 2020-05-15T03:03:20Z
dc.date.issued 2018-09 es_ES
dc.identifier.issn 1757-4676 es_ES
dc.identifier.uri http://hdl.handle.net/10251/143327
dc.description.abstract [EN] 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. es_ES
dc.description.sponsorship We are grateful to D. Megias, L. Martinez, O. Dominguez, F. Al-Shahrour, C. Fustero, O. Graria, G. Garnez-Lapez, A. De Martino, P. Gonzalez, M. Udriste for technical support. Work in the laboratory of R.M.-M was funded by Projects MAT2015-64139-C4-1-R, PROMETE011/2014/047, and by Institute de Salud Carlos III through the project "DTS16/00205" (Co-funded by European Regional Development Fund/European Social Fund "Investing in your future"). Work in the laboratory of M.S. was funded by the CNIO and the IRB, and by grants from the Spanish Ministry of Economy (MINECO, SAF), the European Research Council (ERC Advanced Grant), the Botin Foundation and Banco Santander (Santander Universities Global Division), and by "la Caixa" Foundation. CNIO and IRB Barcelona are recipients of a Severo Ochoa Award of Excellence from the MINECO. D.M.-E was holder of a "Ramon y Cajal" Programme Senior Grant (MINECO, RYC-2013-14471) and was funded by a National Programme for Research Aimed at the Challenges of Society (MINECO, BFU2014-60020-R). Work in the laboratory of D.M.-E. was funded by Cancer Research UK (CRUK, C9685/A25177), and by the CRUK Cambridge Centre Early Detection Programme (RG86786). M.R. was holder of a "la Caixa"-Severo Ochoa PhD scholarship. I.G., B.L.-T., and A.B. were funded by the Generalitat Valenciana and the MINECO. Part of this work has been funded by a research collaboration agreement between Pfizer Inc. and the laboratories of RM.-M. and M.S. The fenders had no role in data collection and analysis, decision to publish, or preparation of the manuscript. es_ES
dc.language Inglés es_ES
dc.publisher EMBO es_ES
dc.relation.ispartof EMBO Molecular Medicine es_ES
dc.rights Reconocimiento (by) es_ES
dc.subject Chemotherapy es_ES
dc.subject Fibrosis es_ES
dc.subject Nanomedicine es_ES
dc.subject Palbociclib es_ES
dc.subject Senescence es_ES
dc.subject.classification QUIMICA ORGANICA es_ES
dc.subject.classification QUIMICA ANALITICA es_ES
dc.subject.classification QUIMICA INORGANICA es_ES
dc.subject.classification BIOQUIMICA Y BIOLOGIA MOLECULAR es_ES
dc.title A versatile drug delivery system targeting senescent cells es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.15252/emmm.201809355 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//RYC-2013-14471/ES/RYC-2013-14471/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//BFU2014-60020-R/ES/LA SENESCENCIA CELULAR COMO COMPONENTE ACTIVO EN LA REMODELACION DE TEJIDOS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/CRUK//C9685%2FA25177/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/GVA//PROMETEOII%2F2014%2F047/ES/Nuevas aproximaciones para el diseño de materiales de liberación controlada y la detección de compuestos peligrosos/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//MAT2015-64139-C4-1-R/ES/NANOMATERIALES INTELIGENTES, SONDAS Y DISPOSITIVOS PARA EL DESARROLLO INTEGRADO DE NUEVAS HERRAMIENTAS APLICADAS AL CAMPO BIOMEDICO/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//DTS16%2F00205/ES/NANODISPOSITIVOS INTELIGENTES DIRIGIDOS A CÉLULAS SENESCENTES: NANO-SEN/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Química - Departament de Química es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Biotecnología - Departament de Biotecnologia es_ES
dc.description.bibliographicCitation Muñoz-Espín, D.; Rovira, M.; Galiana, I.; Giménez Morales, C.; Lozano-Torres, B.; Páez Ribes, M.; Llanos, S.... (2018). A versatile drug delivery system targeting senescent cells. EMBO Molecular Medicine. 10(9). https://doi.org/10.15252/emmm.201809355 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.15252/emmm.201809355 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 10 es_ES
dc.description.issue 9 es_ES
dc.identifier.pmid 30012580 es_ES
dc.identifier.pmcid PMC6127887 es_ES
dc.relation.pasarela S\367864 es_ES
dc.contributor.funder Pfizer es_ES
dc.contributor.funder Fundación Botín es_ES
dc.contributor.funder Cancer Research, Reino Unido es_ES
dc.contributor.funder European Social Fund es_ES
dc.contributor.funder Generalitat Valenciana es_ES
dc.contributor.funder Santander Universidades es_ES
dc.contributor.funder European Research Council es_ES
dc.contributor.funder European Regional Development Fund es_ES
dc.contributor.funder Ministerio de Ciencia y Tecnología es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES
dc.contributor.funder Institute for Research in Biomedicine, España es_ES
dc.contributor.funder Centro Nacional de Investigaciones Oncológicas es_ES
dc.contributor.funder Fundació Bancària Caixa d'Estalvis i Pensions de Barcelona es_ES
dc.description.references Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 51(42), 10556-10560. doi:10.1002/anie.201204663 es_ES
dc.description.references Aoshiba, K., Tsuji, T., & Nagai, A. (2003). Bleomycin induces cellular senescence in alveolar epithelial cells. European Respiratory Journal, 22(3), 436-443. doi:10.1183/09031936.03.00011903 es_ES
dc.description.references Aoshiba, K., Tsuji, T., Kameyama, S., Itoh, M., Semba, S., Yamaguchi, K., & Nakamura, H. (2013). Senescence-associated secretory phenotype in a mouse model of bleomycin-induced lung injury. Experimental and Toxicologic Pathology, 65(7-8), 1053-1062. doi:10.1016/j.etp.2013.04.001 es_ES
dc.description.references Aznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456 es_ES
dc.description.references Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., … de Keizer, P. L. J. (2017). Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169(1), 132-147.e16. doi:10.1016/j.cell.2017.02.031 es_ES
dc.description.references Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., … van Deursen, J. M. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 530(7589), 184-189. doi:10.1038/nature16932 es_ES
dc.description.references Barry, S. P., Davidson, S. M., & Townsend, P. A. (2008). Molecular regulation of cardiac hypertrophy. The International Journal of Biochemistry & Cell Biology, 40(10), 2023-2039. doi:10.1016/j.biocel.2008.02.020 es_ES
dc.description.references Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499d es_ES
dc.description.references Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., … Zhou, D. (2015). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature Medicine, 22(1), 78-83. doi:10.1038/nm.4010 es_ES
dc.description.references Chatterjee, K., Zhang, J., Honbo, N., & Karliner, J. S. (2010). Doxorubicin Cardiomyopathy. Cardiology, 115(2), 155-162. doi:10.1159/000265166 es_ES
dc.description.references Chiche, A., Le Roux, I., von Joest, M., Sakai, H., Aguín, S. B., Cazin, C., … Li, H. (2017). Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle. Cell Stem Cell, 20(3), 407-414.e4. doi:10.1016/j.stem.2016.11.020 es_ES
dc.description.references Childs, B. G., Baker, D. J., Wijshake, T., Conover, C. A., Campisi, J., & van Deursen, J. M. (2016). Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science, 354(6311), 472-477. doi:10.1126/science.aaf6659 es_ES
dc.description.references Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017). Senescent cells: an emerging target for diseases of ageing. Nature Reviews Drug Discovery, 16(10), 718-735. doi:10.1038/nrd.2017.116 es_ES
dc.description.references Cho, J.-H., Saini, D. K., Karunarathne, W. K. A., Kalyanaraman, V., & Gautam, N. (2011). Alteration of Golgi structure in senescent cells and its regulation by a G protein γ subunit. Cellular Signalling, 23(5), 785-793. doi:10.1016/j.cellsig.2011.01.001 es_ES
dc.description.references Collado, M., & Serrano, M. (2010). Senescence in tumours: evidence from mice and humans. Nature Reviews Cancer, 10(1), 51-57. doi:10.1038/nrc2772 es_ES
dc.description.references Demaria, M., Ohtani, N., Youssef, S. A., Rodier, F., Toussaint, W., Mitchell, J. R., … Campisi, J. (2014). An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA. Developmental Cell, 31(6), 722-733. doi:10.1016/j.devcel.2014.11.012 es_ES
dc.description.references Demaria, M., O’Leary, M. N., Chang, J., Shao, L., Liu, S., Alimirah, F., … Campisi, J. (2016). Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discovery, 7(2), 165-176. doi:10.1158/2159-8290.cd-16-0241 es_ES
dc.description.references Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., … Pereira-Smith, O. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences, 92(20), 9363-9367. doi:10.1073/pnas.92.20.9363 es_ES
dc.description.references Gewirtz, D. (1999). A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochemical Pharmacology, 57(7), 727-741. doi:10.1016/s0006-2952(98)00307-4 es_ES
dc.description.references Giefing, M., Zemke, N., Brauze, D., Kostrzewska-Poczekaj, M., Luczak, M., Szaumkessel, M., … Jarmuz, M. (2010). High resolution ArrayCGH and expression profiling identifies PTPRD and PCDH17/PCH68 as tumor suppressor gene candidates in laryngeal squamous cell carcinoma. Genes, Chromosomes and Cancer, 50(3), 154-166. doi:10.1002/gcc.20840 es_ES
dc.description.references Hall, B. M., Balan, V., Gleiberman, A. S., Strom, E., Krasnov, P., Virtuoso, L. P., … Gudkov, A. V. (2017). p16(Ink4a) and senescence-associated β-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging, 9(8), 1867-1884. doi:10.18632/aging.101268 es_ES
dc.description.references Hecker, L., Logsdon, N. J., Kurundkar, D., Kurundkar, A., Bernard, K., Hock, T., … Thannickal, V. J. (2014). Reversal of Persistent Fibrosis in Aging by Targeting Nox4-Nrf2 Redox Imbalance. Science Translational Medicine, 6(231), 231ra47-231ra47. doi:10.1126/scitranslmed.3008182 es_ES
dc.description.references Hocine, O., Gary-Bobo, M., Brevet, D., Maynadier, M., Fontanel, S., Raehm, L., … Frochot, C. (2010). Silicalites and Mesoporous Silica Nanoparticles for photodynamic therapy. International Journal of Pharmaceutics, 402(1-2), 221-230. doi:10.1016/j.ijpharm.2010.10.004 es_ES
dc.description.references Ikediobi, O. N., Davies, H., Bignell, G., Edkins, S., Stevens, C., O’Meara, S., … Wooster, R. (2006). Mutation analysis of 24 known cancer genes in the NCI-60 cell line set. Molecular Cancer Therapeutics, 5(11), 2606-2612. doi:10.1158/1535-7163.mct-06-0433 es_ES
dc.description.references Ivanov, A., Pawlikowski, J., Manoharan, I., van Tuyn, J., Nelson, D. M., Rai, T. S., … Adams, P. D. (2013). Lysosome-mediated processing of chromatin in senescence. Journal of Cell Biology, 202(1), 129-143. doi:10.1083/jcb.201212110 es_ES
dc.description.references Kile, B. T. (2014). The role of apoptosis in megakaryocytes and platelets. British Journal of Haematology, 165(2), 217-226. doi:10.1111/bjh.12757 es_ES
dc.description.references Kresge, C. T., Leonowicz, M. E., Roth, W. J., Vartuli, J. C., & Beck, J. S. (1992). Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature, 359(6397), 710-712. doi:10.1038/359710a0 es_ES
dc.description.references Krizhanovsky, V., Yon, M., Dickins, R. A., Hearn, S., Simon, J., Miething, C., … Lowe, S. W. (2008). Senescence of Activated Stellate Cells Limits Liver Fibrosis. Cell, 134(4), 657-667. doi:10.1016/j.cell.2008.06.049 es_ES
dc.description.references Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009). Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biology, 10(3), R25. doi:10.1186/gb-2009-10-3-r25 es_ES
dc.description.references Lasry, A., & Ben-Neriah, Y. (2015). Senescence-associated inflammatory responses: aging and cancer perspectives. Trends in Immunology, 36(4), 217-228. doi:10.1016/j.it.2015.02.009 es_ES
dc.description.references Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., … Hwang, E. S. (2006). Senescence-associated β-galactosidase is lysosomal β-galactosidase. Aging Cell, 5(2), 187-195. doi:10.1111/j.1474-9726.2006.00199.x es_ES
dc.description.references Li, W., Fan, J., Hochhauser, D., Banerjee, D., Zielinski, Z., Almasan, A., … Bertino, J. R. (1995). Lack of functional retinoblastoma protein mediates increased resistance to antimetabolites in human sarcoma cell lines. Proceedings of the National Academy of Sciences, 92(22), 10436-10440. doi:10.1073/pnas.92.22.10436 es_ES
dc.description.references Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., … Homer, N. (2009). The Sequence Alignment/Map format and SAMtools. Bioinformatics, 25(16), 2078-2079. doi:10.1093/bioinformatics/btp352 es_ES
dc.description.references Love, M. I., Huber, W., & Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15(12). doi:10.1186/s13059-014-0550-8 es_ES
dc.description.references Massaro, R. R., Faião-Flores, F., Rebecca, V. W., Sandri, S., Alves-Fernandes, D. K., Pennacchi, P. C., … Maria-Engler, S. S. (2017). Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells. Pharmacological Research, 119, 242-250. doi:10.1016/j.phrs.2017.02.013 es_ES
dc.description.references Mosteiro, L., Pantoja, C., Alcazar, N., Marión, R. M., Chondronasiou, D., Rovira, M., … Serrano, M. (2016). Tissue damage and senescence provide critical signals for cellular reprogramming in vivo. Science, 354(6315), aaf4445. doi:10.1126/science.aaf4445 es_ES
dc.description.references Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., … Serrano, M. (2013). Programmed Cell Senescence during Mammalian Embryonic Development. Cell, 155(5), 1104-1118. doi:10.1016/j.cell.2013.10.019 es_ES
dc.description.references Muñoz-Espín, D., & Serrano, M. (2014). Cellular senescence: from physiology to pathology. Nature Reviews Molecular Cell Biology, 15(7), 482-496. doi:10.1038/nrm3823 es_ES
dc.description.references Nair, J. B., Mohapatra, S., Ghosh, S., & Maiti, K. K. (2015). Novel lysosome targeted molecular transporter built on a guanidinium-poly-(propylene imine) hybrid dendron for efficient delivery of doxorubicin into cancer cells. Chemical Communications, 51(12), 2403-2406. doi:10.1039/c4cc09829c es_ES
dc.description.references Narita, M., Young, A. R. J., Arakawa, S., Samarajiwa, S. A., Nakashima, T., Yoshida, S., … Narita, M. (2011). Spatial Coupling of mTOR and Autophagy Augments Secretory Phenotypes. Science, 332(6032), 966-970. doi:10.1126/science.1205407 es_ES
dc.description.references Pan, J., Li, D., Xu, Y., Zhang, J., Wang, Y., Chen, M., … Meng, A. (2017). Inhibition of Bcl-2/xl With ABT-263 Selectively Kills Senescent Type II Pneumocytes and Reverses Persistent Pulmonary Fibrosis Induced by Ionizing Radiation in Mice. International Journal of Radiation Oncology*Biology*Physics, 99(2), 353-361. doi:10.1016/j.ijrobp.2017.02.216 es_ES
dc.description.references Richard, C., Ghibu, S., Delemasure-Chalumeau, S., Guilland, J.-C., Des Rosiers, C., Zeller, M., … Vergely, C. (2011). Oxidative Stress and Myocardial Gene Alterations Associated with Doxorubicin-Induced Cardiotoxicity in Rats Persist for 2 Months after Treatment Cessation. Journal of Pharmacology and Experimental Therapeutics, 339(3), 807-814. doi:10.1124/jpet.111.185892 es_ES
dc.description.references Ritschka, B., Storer, M., Mas, A., Heinzmann, F., Ortells, M. C., Morton, J. P., … Keyes, W. M. (2017). The senescence-associated secretory phenotype induces cellular plasticity and tissue regeneration. Genes & Development, 31(2), 172-183. doi:10.1101/gad.290635.116 es_ES
dc.description.references Roos, C. M., Zhang, B., Palmer, A. K., Ogrodnik, M. B., Pirtskhalava, T., Thalji, N. M., … Miller, J. D. (2016). Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell, 15(5), 973-977. doi:10.1111/acel.12458 es_ES
dc.description.references Schafer, M. J., White, T. A., Iijima, K., Haak, A. J., Ligresti, G., Atkinson, E. J., … LeBrasseur, N. K. (2017). Cellular senescence mediates fibrotic pulmonary disease. Nature Communications, 8(1). doi:10.1038/ncomms14532 es_ES
dc.description.references Sharpless, N. E., & Sherr, C. J. (2015). Forging a signature of in vivo senescence. Nature Reviews Cancer, 15(7), 397-408. doi:10.1038/nrc3960 es_ES
dc.description.references Sheng, Y., Xu, J., You, Y., Xu, F., & Chen, Y. (2015). Acid-Sensitive Peptide-Conjugated Doxorubicin Mediates the Lysosomal Pathway of Apoptosis and Reverses Drug Resistance in Breast Cancer. Molecular Pharmaceutics, 12(7), 2217-2228. doi:10.1021/mp500386y es_ES
dc.description.references Slowing, I., Trewyn, B. G., & Lin, V. S.-Y. (2006). Effect of Surface Functionalization of MCM-41-Type Mesoporous Silica Nanoparticles on the Endocytosis by Human Cancer Cells. Journal of the American Chemical Society, 128(46), 14792-14793. doi:10.1021/ja0645943 es_ES
dc.description.references Slowing, I. I., Vivero-Escoto, J. L., Zhao, Y., Kandel, K., Peeraphatdit, C., Trewyn, B. G., & Lin, V. S.-Y. (2011). Exocytosis of Mesoporous Silica Nanoparticles from Mammalian Cells: From Asymmetric Cell-to-Cell Transfer to Protein Harvesting. Small, 7(11), 1526-1532. doi:10.1002/smll.201002077 es_ES
dc.description.references Soto-Gamez, A., & Demaria, M. (2017). Therapeutic interventions for aging: the case of cellular senescence. Drug Discovery Today, 22(5), 786-795. doi:10.1016/j.drudis.2017.01.004 es_ES
dc.description.references Storer, M., Mas, A., Robert-Moreno, A., Pecoraro, M., Ortells, M. C., Di Giacomo, V., … Keyes, W. M. (2013). Senescence Is a Developmental Mechanism that Contributes to Embryonic Growth and Patterning. Cell, 155(5), 1119-1130. doi:10.1016/j.cell.2013.10.041 es_ES
dc.description.references Tai, H., Wang, Z., Gong, H., Han, X., Zhou, J., Wang, X., … Xiao, H. (2016). Autophagy impairment with lysosomal and mitochondrial dysfunction is an important characteristic of oxidative stress-induced senescence. Autophagy, 13(1), 99-113. doi:10.1080/15548627.2016.1247143 es_ES
dc.description.references Tao, Z., Toms, B. B., Goodisman, J., & Asefa, T. (2009). Mesoporosity and Functional Group Dependent Endocytosis and Cytotoxicity of Silica Nanomaterials. Chemical Research in Toxicology, 22(11), 1869-1880. doi:10.1021/tx900276u es_ES
dc.description.references Trapnell, C., Roberts, A., Goff, L., Pertea, G., Kim, D., Kelley, D. R., … Pachter, L. (2012). Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nature Protocols, 7(3), 562-578. doi:10.1038/nprot.2012.016 es_ES
dc.description.references Wilhelm, S., Tavares, A. J., Dai, Q., Ohta, S., Audet, J., Dvorak, H. F., & Chan, W. C. W. (2016). Analysis of nanoparticle delivery to tumours. Nature Reviews Materials, 1(5). doi:10.1038/natrevmats.2016.14 es_ES
dc.description.references Yanes, R. E., Tarn, D., Hwang, A. A., Ferris, D. P., Sherman, S. P., Thomas, C. R., … Tamanoi, F. (2012). Involvement of Lysosomal Exocytosis in the Excretion of Mesoporous Silica Nanoparticles and Enhancement of the Drug Delivery Effect by Exocytosis Inhibition. Small, 9(5), 697-704. doi:10.1002/smll.201201811 es_ES
dc.description.references Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., … Krizhanovsky, V. (2016). Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nature Communications, 7(1). doi:10.1038/ncomms11190 es_ES
dc.description.references Yun, M. H., Davaapil, H., & Brockes, J. P. (2015). Recurrent turnover of senescent cells during regeneration of a complex structure. eLife, 4. doi:10.7554/elife.05505 es_ES
dc.description.references Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … Kirkland, J. L. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 14(4), 644-658. doi:10.1111/acel.12344 es_ES
dc.description.references Zhu, Y., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., … Kirkland, J. L. (2016). Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors. Aging Cell, 15(3), 428-435. doi:10.1111/acel.12445 es_ES


Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem