Exploration of mechanism of anticancer potential of fisetin nanoformulations: nanotized fisetin/fisetin loaded polymannose nanoparticles in the treatment of triple negative breast carcinoma.

IF 2.9 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2025-08-01 Epub Date: 2025-07-24 DOI:10.1007/s13205-025-04427-x

Neena Yadav, Saswat Kumar Mohanty, Sathyapriya Chandramohan, V K Archana, Kitlangki Suchiang, Rukkumani Rajagopalan

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引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) remains one of the most aggressive and difficult-to-treat subtypes of breast cancer due to the lack of targeted therapies. This study investigates the anti-proliferative and anti-metastatic potential of fisetin (FIS) and its nanoformulations, nanotized fisetin (Nano-FIS) and FIS-loaded polymannose nanoparticles (FIS-PM NPs) in TNBC cells. Both Nano-FIS and FIS-PM NPs demonstrated significant, time- and dose-dependent cytotoxicity, with FIS-PM NPs showing the greatest inhibition of cell viability. Morphological assessments revealed pronounced apoptotic features, including cell shrinkage and rounding, particularly in nanoformulation-treated cells. In vitro wound healing assays confirmed that Nano-FIS and FIS-PM NPs markedly delayed cell migration compared to free FIS, indicating strong anti-metastatic properties. Western blot analysis further revealed that treatment with the nanoformulations downregulated pro-survival proteins NF-κB p65, Cyclin D1, and Bcl-2, while upregulating pro-apoptotic proteins Caspase-3 and Caspase-8, with FIS-PM NPs eliciting the most pronounced effects. RT-PCR analysis supported these findings by demonstrating significant downregulation of angiogenesis- and metastasis-related genes VEGF-A, VCAM1, MMP-9, and MMP-2 in nanoformulation-treated TNBC cells. Overall, the results suggest that FIS-based nanoformulations, particularly FIS-PM NPs, exhibit enhanced anti-cancer efficacy through the induction of apoptosis, inhibition of cell proliferation, migration, and angiogenesis, making them promising therapeutic candidates for TNBC treatment.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04427-x.

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非瑟酮纳米制剂抗癌潜力机制的探索：纳米化非瑟酮/负载非瑟酮的聚甘露糖纳米颗粒治疗三阴性乳腺癌。

由于缺乏靶向治疗，三阴性乳腺癌（TNBC）仍然是最具侵袭性和最难治疗的乳腺癌亚型之一。本研究探讨了非瑟酮（FIS）及其纳米制剂、纳米化非瑟酮（Nano-FIS）和负载非瑟酮的聚甘露糖纳米颗粒（fiss - pm NPs）在TNBC细胞中的抗增殖和抗转移潜力。纳米fis和FIS-PM NPs均表现出显著的时间和剂量依赖性细胞毒性，其中FIS-PM NPs对细胞活力的抑制作用最大。形态学评估显示明显的凋亡特征，包括细胞收缩和圆圆，特别是在纳米配方处理的细胞中。体外伤口愈合实验证实，与游离FIS相比，纳米FIS和FIS- pm NPs显著延缓了细胞迁移，显示出强大的抗转移特性。Western blot分析进一步显示，纳米制剂下调促存活蛋白NF-κB p65、Cyclin D1和Bcl-2，上调促凋亡蛋白Caspase-3和Caspase-8，其中FIS-PM NPs的作用最为明显。RT-PCR分析证实了纳米制剂处理的TNBC细胞中血管生成和转移相关基因VEGF-A、VCAM1、MMP-9和MMP-2的显著下调，从而支持了这些发现。总体而言，研究结果表明，基于fis的纳米制剂，特别是FIS-PM NPs，通过诱导细胞凋亡、抑制细胞增殖、迁移和血管生成，表现出增强的抗癌功效，使其成为TNBC治疗的有希望的治疗候选者。补充信息：在线版本包含补充资料，提供地址为10.1007/s13205-025-04427-x。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.