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用脂质体包裹的漆黄素靶向细胞衰老:衰老形态效应的证据。

Targeting Cellular Senescence with Liposome-Encapsulated Fisetin: Evidence of Senomorphic Effect.

作者信息

Henschke Agata, Grześkowiak Bartosz, Ivashchenko Olena, Sánchez-Cerviño María Celina, Coy Emerson, Moya Sergio

机构信息

NanoBioMedical Centre, Adam Mickiewicz University, Wszechnicy Piastowskiej 3, 61-614 Poznan, Poland.

Biomedical Polymers Division, Research Institute for Materials Science and Technology (INTEMA), National University of Mar del Plata (UNMdP)-National Scientific and Technical Research Council (CONICET), Av. Colón 10850, Mar del Plata 7600, Argentina.

出版信息

Int J Mol Sci. 2025 Aug 2;26(15):7489. doi: 10.3390/ijms26157489.


DOI:10.3390/ijms26157489
PMID:40806616
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347707/
Abstract

Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin's hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin's therapeutic efficacy, showing comparable results even at the lowest tested concentration.

摘要

细胞衰老与癌症进展、复发和转移密切相关。衰老疗法旨在通过诱导衰老细胞凋亡(衰老溶解)或抑制衰老相关分泌表型(SASP)(衰老形态改变)来缓解衰老细胞的有害影响。漆黄素是一种经过充分研究的衰老治疗药物,本研究选用它来评估其脂质体制剂的疗效。该实验评估了脂质体包裹的漆黄素对两种细胞系(WI-38(正常肺成纤维细胞)和A549(肺癌细胞))中由阿霉素(DOX)诱导的衰老细胞的影响。通过衰老相关β-半乳糖苷酶(SA-β-gal)活性、增殖、形态以及促炎白细胞介素6(IL-6)和白细胞介素8(IL-8)的分泌来表征衰老。由于漆黄素的疏水性,将其包裹在脂质体中以增强细胞递送。细胞摄取研究证实,两种衰老细胞类型均能有效内化脂质体。用负载漆黄素的脂质体处理显示缺乏衰老溶解作用,但表现出衰老形态改变活性,衰老细胞中IL-6和IL-8分泌显著减少证明了这一点。脂质体制剂提高了漆黄素的治疗效果,即使在最低测试浓度下也显示出可比的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/05d8f140757a/ijms-26-07489-g012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/5a81cc71c28d/ijms-26-07489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/6e55fc93fb1b/ijms-26-07489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/a02e16facd43/ijms-26-07489-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/7c2158ee41ef/ijms-26-07489-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/db0e727f2c0d/ijms-26-07489-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/93622231bb53/ijms-26-07489-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/809429c6f2de/ijms-26-07489-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/067fce8467ac/ijms-26-07489-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/05d8f140757a/ijms-26-07489-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/bddb4301a1d9/ijms-26-07489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/a36361faf315/ijms-26-07489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/a7a5032ae806/ijms-26-07489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/5a81cc71c28d/ijms-26-07489-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/6e55fc93fb1b/ijms-26-07489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/a02e16facd43/ijms-26-07489-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/7c2158ee41ef/ijms-26-07489-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/db0e727f2c0d/ijms-26-07489-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/93622231bb53/ijms-26-07489-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/809429c6f2de/ijms-26-07489-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/067fce8467ac/ijms-26-07489-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/300f/12347707/05d8f140757a/ijms-26-07489-g012.jpg

相似文献

[1]
Targeting Cellular Senescence with Liposome-Encapsulated Fisetin: Evidence of Senomorphic Effect.

Int J Mol Sci. 2025-8-2

[2]
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[3]
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[4]
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[6]
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[7]
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[10]
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本文引用的文献

[1]
Single-cell morphology encodes functional subtypes of senescence in aging human dermal fibroblasts.

Sci Adv. 2025-4-25

[2]
Fisetin Clears Senescent Cells Through the Pi3k-Akt-Bcl-2/Bcl-xl Pathway to Alleviate Diabetic Aortic Aging.

Phytother Res. 2025-4-21

[3]
Therapy-Induced Senescence: Novel Approaches for Markers Identification.

Int J Mol Sci. 2024-8-2

[4]
A review of the pathophysiological mechanisms of doxorubicin-induced cardiotoxicity and aging.

NPJ Aging. 2024-1-23

[5]
Morphology-based deep learning enables accurate detection of senescence in mesenchymal stem cell cultures.

BMC Biol. 2024-1-2

[6]
Nuclear morphology is a deep learning biomarker of cellular senescence.

Nat Aging. 2022-8

[7]
Liposomes loaded with quercetin for resolution of lung inflammation in a lipopolysaccharide-induced mouse model of sepsis.

Biomed Mater. 2023-3-13

[8]
Electrohydrodynamic Techniques for the Manufacture and/or Immobilization of Vesicles.

Polymers (Basel). 2023-2-4

[9]
Systematic modulation of the lipid composition enables the tuning of liposome cellular uptake.

Acta Biomater. 2023-3-1

[10]
Liposomes: structure, composition, types, and clinical applications.

Heliyon. 2022-5-13

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