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<p>Etoposide is a widely used chemotherapeutic agent whose clinical application is limited by systemic toxicity and suboptimal intracellular delivery. Lipid-polymer hybrid nanoparticles have emerged as promising drug delivery systems that combine structural stability with enhanced cellular interaction. This study aimed to evalute the apoptotic and metastasis-related effects of etoposide-loaded lipid-polymer hybrid nanoparticles (ET-NPs) against human breast cancer cells. ET-NPs were synthesized and characterized, and their biological effects were compared with free etoposide in MCF-7 and MDA-MB-231 breast cancer cell lines. Cell viability was assessed using the MTT assay. Cell cycle distribution, Annexin V binding activity, mitochondrial membrane potential, and caspase activation were analyzed by flow cytometry based Muse Cell Analyzer. MMP-2 and MMP-9 mRNA levels were determined by quantitative real-time PCR. ET-NPs significantly enhanced the cytotoxic and pro-apoptotic effects of etoposide in both breast cancer cell lines. Annexin V analysis demonstrated increased apoptotic cell populations following ET-NP treatment compared with free etoposide. ET-NP also induced significant mitochondrial membrane depolarization, caspase activation, and G2/M phase arrest. Furthermore, ET-NP significantly exerted potential anti-metastatic activity indicating a preferential antitumor effect in MCF-7 cells compared with MDA-MB-231 cells. The findings of this study demonstrate that lipid-polymer hybrid nanoparticle-mediated delivery enhances the anticancer efficacy of etoposide in breast cancer cells by potentiating apoptotic signaling and suppressing metastasis-related gene expression. ET-NP may therefore represent a promising nanotherapeutic strategy for improving breast cancer treatment outcomes.</p>

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Preferential enhancement of mitochondria-mediated apoptosis and modulation of metastasis-related markers by etoposide-loaded nanoparticles in breast cancer cell lines

  • 期刊论文

  • 发表日期：

    2026年7月4日

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  • Filiz Bakar-Ates,
  • Ceyda Tuba Sengel-Turk

摘要

Etoposide is a widely used chemotherapeutic agent whose clinical application is limited by systemic toxicity and suboptimal intracellular delivery. Lipid-polymer hybrid nanoparticles have emerged as promising drug delivery systems that combine structural stability with enhanced cellular interaction. This study aimed to evalute the apoptotic and metastasis-related effects of etoposide-loaded lipid-polymer hybrid nanoparticles (ET-NPs) against human breast cancer cells. ET-NPs were synthesized and characterized, and their biological effects were compared with free etoposide in MCF-7 and MDA-MB-231 breast cancer cell lines. Cell viability was assessed using the MTT assay. Cell cycle distribution, Annexin V binding activity, mitochondrial membrane potential, and caspase activation were analyzed by flow cytometry based Muse Cell Analyzer. MMP-2 and MMP-9 mRNA levels were determined by quantitative real-time PCR. ET-NPs significantly enhanced the cytotoxic and pro-apoptotic effects of etoposide in both breast cancer cell lines. Annexin V analysis demonstrated increased apoptotic cell populations following ET-NP treatment compared with free etoposide. ET-NP also induced significant mitochondrial membrane depolarization, caspase activation, and G2/M phase arrest. Furthermore, ET-NP significantly exerted potential anti-metastatic activity indicating a preferential antitumor effect in MCF-7 cells compared with MDA-MB-231 cells. The findings of this study demonstrate that lipid-polymer hybrid nanoparticle-mediated delivery enhances the anticancer efficacy of etoposide in breast cancer cells by potentiating apoptotic signaling and suppressing metastasis-related gene expression. ET-NP may therefore represent a promising nanotherapeutic strategy for improving breast cancer treatment outcomes.