Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles

Agostini, Alessandro; Mondragón, Laura; Bernardos, Andrea; Martínez‐Máñez, Ramón; Marcos, M. Dolores; Sancenón, Félix; Soto, Juán; Costero, Ana M.; Manguán-García, Cristina; Perona, Rosario; Moreno-Torres, Marta; Aparicio-Sanchis, Rafael; Murguía, José Ramón

doi:10.1002/ange.201204663

Cited by 41 publications

(38 citation statements)

References 41 publications

(32 reference statements)

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“…This approach has been employed to activate mesoporous silica nanoparticles coated with galacto-oligosaccharide, which is a substrate of the senescent biomarker SA-β-Gal. In senescent X-linked diskeratosis congenita cells that express SA-β-Gal, the galacto-oligosaccharide is cleaved, which releases rhodamine packaged within the silica nanoparticles 155 . Similar activation of a prodrug could be achieved extracellularly by enzymes that are part of the SASP.…”

Section: Therapeutic Considerations and Challengesmentioning

confidence: 99%

Senescent cells: an emerging target for diseases of ageing

Childs

Gluscevic

Baker

et al. 2017

Nat Rev Drug Discov

905

797

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Chronological age represents the single greatest risk factor for human disease. One plausible explanation for this correlation is that mechanisms that drive ageing might also promote age-related diseases. Cellular senescence, which is a permanent state of cell cycle arrest induced by cellular stress, has recently emerged as a fundamental ageing mechanism that also contributes to diseases of late life, including cancer, atherosclerosis and osteoarthritis. Therapeutic strategies that safely interfere with the detrimental effects of cellular senescence, such as the selective elimination of senescent cells (SNCs) or the disruption of the SNC secretome, are gaining significant attention, with several programmes now nearing human clinical studies.

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Section: Therapeutic Considerations and Challengesmentioning

confidence: 99%

Senescent cells: an emerging target for diseases of ageing

Childs

Gluscevic

Baker

et al. 2017

Nat Rev Drug Discov

905

797

View full text Add to dashboard Cite

show abstract

“…The first steps into this brave new world have been taken and, recently, an intelligent system has been devised that lays the foundations for the future development of new therapies against aging. This nanodevice consists of capped silica nanoparticles that can selectively release drugs in aged human cells (Agostini et al, 2012) and has enormous potential in the treatment of a myriad of diseases, namely, cancer or Alzheimer's. Hence, there is a promise that nanostructures of the like will be able to drive chemical reactions that are capable of slowing down or even reverse senescence, by reversing the chemical reactions and damage that take place with aging.…”

Section: Aging Therapies—cure Aging or Die Trying?mentioning

confidence: 99%

A synopsis on aging—Theories, mechanisms and future prospects

Costa

Vitorino

Silva³

et al. 2016

Ageing Research Reviews

328

170

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Answering the question as to why we age is tantamount to answering the question of what is life itself. There are countless theories as to why and how we age, but, until recently, the very definition of aging – senescence – was still uncertain. Here, we summarize the main views of the different models of senescence, with a special emphasis on the biochemical processes that accompany aging. Though inherently complex, aging is characterized by numerous changes that take place at different levels of the biological hierarchy. We therefore explore some of the most relevant changes that take place during aging and, finally, we overview the current status of emergent aging therapies and what the future holds for this field of research. From this multi-dimensional approach, it becomes clear that an integrative approach that couples aging research with systems biology, capable of providing novel insights into how and why we age, is necessary.

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“…Another emerging possibility to increase specificity is to modify the therapeutic or diagnostic agent to be activated by an external stimulus or enzymatic reaction. This is the case for galactose‐based nanoparticles, encapsulation methods and probes (Agostini et al , ; Lozano‐Torres et al , ; Thapa et al , ; Muñoz‐Espín et al , ), which are preferentially activated by the increased lysosomal β‐gal function of senescent cells. Alternatively, accumulation of SASP components and enzymes in the senescent intercellular space might also be employed to stimulate drug delivery systems and inactive pro‐senolytics, or activatable probes, for imaging.…”

Section: Introductionmentioning

confidence: 99%

Targeting senescent cells in translational medicine

et al. 2019

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Organismal ageing is a complex process driving progressive impairment of functionality and regenerative potential of tissues. Cellular senescence is a state of stable cell cycle arrest occurring in response to damage and stress and is considered a hallmark of ageing. Senescent cells accumulate in multiple organs during ageing, contribute to tissue dysfunction and give rise to pathological manifestations. Senescence is therefore a defining feature of a variety of human age‐related disorders, including cancer, and targeted elimination of these cells has recently emerged as a promising therapeutic approach to ameliorate tissue damage and promote repair and regeneration. In addition, in vivo identification of senescent cells has significant potential for early diagnosis of multiple pathologies. Here, we review existing senolytics, small molecules and drug delivery tools used in preclinical therapeutic strategies involving cellular senescence, as well as probes to trace senescent cells. We also review the clinical research landscape in senescence and discuss how identifying and targeting cellular senescence might positively affect pathological and ageing processes.

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Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles

Cited by 41 publications

References 41 publications

Senescent cells: an emerging target for diseases of ageing

Senescent cells: an emerging target for diseases of ageing

A synopsis on aging—Theories, mechanisms and future prospects

Targeting senescent cells in translational medicine

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