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Analysis of institutional authors

García-Fleitas, JAuthorMartí-Centelles, VAuthorSancenon, FAuthorBernardos, ACorresponding AuthorMartínez-Máñez, RCorresponding Author

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October 11, 2024
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Chemical Strategies for the Detection and Elimination of Senescent Cells

Publicated to:Accounts Of Chemical Research. 57 (9): 1238-1253 - 2024-04-11 57(9), DOI: 10.1021/acs.accounts.3c00794

Authors: Garcia-Fleitas, Jessie; Garcia-Fernandez, Alba; Marti-Centelles, Vicente; Sancenon, Felix; Bernardos, Andrea; Martinez-Manez, Ramon

Affiliations

Univ Politecn Valencia, Ctr Invest Principe Felipe, Unidad Mixta UPV CIPF Invest Mecan Enfermedades & - Author
Univ Politecn Valencia, Dept Quim - Author
Univ Politecn Valencia, Unidad Mixta Invest Nanomed & Sensores, Inst Invest Sanitaria La Fe - Author
Univ Valencia, Univ Politecn Valencia, Inst Interuniv Invest Reconocimiento Mol & Desarr - Author

Abstract

Cellular senescence can be defined as an irreversible stopping of cell proliferation that arises in response to various stress signals. Cellular senescence is involved in diverse physiological and pathological processes in different tissues, exerting effects on processes as differentiated as embryogenesis, tissue repair and remodeling, cancer, aging, and tissue fibrosis. In addition, the development of some pathologies, aging, cancer, and other age-related diseases has been related to senescent cell accumulation. Due to the complexity of the senescence phenotype, targeting senescent cells is not trivial, is challenging, and is especially relevant for in vivo detection in age-related diseases and tissue samples. Despite the elimination of senescent cells (senolysis) using specific drugs (senolytics) that have been shown to be effective in numerous preclinical disease models, the clinical translation is still limited due to the off-target effects of current senolytics and associated toxicities. Therefore, the development of new chemical strategies aimed at detecting and eliminating senescent cells for the prevention and selective treatment of senescence-associated diseases is of great interest. Such strategies not only will contribute to a deeper understanding of this rapidly evolving field but also will delineate and inspire new possibilities for future research. In this Account, we report our recent research in the development of new chemical approaches for the detection and elimination of senescent cells based on new probes, nanoparticles, and prodrugs. The designed systems take advantage of the over-representation in senescent cells of certain biomarkers such as beta-galactosidase and lipofuscin. One- and two-photon probes, for higher tissue penetration, have been developed. Moreover, we also present a renal clearable fluorogenic probe for the in vivo detection of the beta-galactosidase activity, allowing for correlation with the senescent burden in living animals. Moreover, as an alternative to molecular-based probes, we also developed nanoparticles for senescence detection. Besides, we describe advances in new therapeutic agents to selectively eradicate senescent cells using beta-galactosidase activity-sensitive gated nanoparticles loaded with cytotoxic or senolytic agents or new prodrugs aiming to increase the selectivity and reduction of off-target toxicities of current drugs. Moreover, new advances therapies have been applied in vitro and in vivo. Studies with the probes, nanoparticles, and prodrugs have been applied in several in vitro and in vivo models of cancer, fibrosis, aging, and drug-induced cardiotoxicity in which senescence plays an important role. We discuss the benefits of these chemical strategies toward the development of more specific and sophisticated probes, nanoparticles, and prodrugs targeting senescent cells.

Keywords

AnimalsBeta-galactosidaseCancerCellular senescenceDoxorubicinFluorescent-probeHumansMechanismsReleaseSenotherapeuticsTrackingTumor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Accounts Of Chemical Research due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 13/231, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-07-08:

  • WoS: 15
  • Scopus: 7
  • Europe PMC: 5

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-08:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 22.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 25 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.05.
  • The number of mentions on the social network X (formerly Twitter): 13 (Altmetric).

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (García Fleitas, Jessie) and Last Author (Martínez Mañez, Ramón).

the authors responsible for correspondence tasks have been García-Fernández, A, Bernardos Bau, Andrea and Martínez Mañez, Ramón.