Henschke Agata, Grześkowiak Bartosz, Ivashchenko Olena, Sánchez-Cerviño María Celina, Coy Emerson, Moya Sergio
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.
Int J Mol Sci. 2025 Aug 2;26(15):7489. doi: 10.3390/ijms26157489.
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.
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。
Int J Mol Sci. 2024-8-2
Polymers (Basel). 2023-2-4
Heliyon. 2022-5-13