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白蛋白纳米颗粒介导的阿霉素递送通过控释提高卵巢癌细胞的抗肿瘤效率。

Albumin nanoparticles-mediated doxorubicin delivery enhances the anti-tumor efficiency in ovarian cancer cells through controlled release.

作者信息

Masoumi Sajjad, Aleyasin Seyed Ahmad, Faghihi Shahab

机构信息

Department of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

Stem Cell and Regenerative Medicine Group, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun;398(6):6885-6900. doi: 10.1007/s00210-024-03730-3. Epub 2024 Dec 18.

Abstract

Doxorubicin (DOX) is an anthracycline commonly used as a first-line treatment option for various malignancies, either as a stand-alone treatment or in combination with other chemotherapeutic agents. However, its efficacy in advanced cancer stages requires high doses, resulting in significant cytotoxicity to normal cells and severe side effects. Nanotechnology offers a promising strategy to mitigate these drawbacks through controlled drug release. In this study, bovine serum albumin nanoparticles (BSA-NPs) were synthesized via the desolvation method and successfully loaded with DOX (DOX-BSA-NPs). Characterization using dynamic light scattering, scanning electron microscopy, Fourier-transform infrared spectroscopy, UV-visible spectroscopy, and high-performance liquid chromatography confirmed efficient drug loading. In vitro studies demonstrated that DOX-BSA-NPs enabled sustained drug release and enhanced intracellular delivery. After treatment with DOX-BSA-NPs, ovarian cancer cells showed a twofold increase in cytotoxicity compared to free DOX. Scratch assays further revealed a significant reduction in cancer cell migration and invasion. Additionally, LDH assays and Annexin V-FITC flow cytometry indicated a shift toward apoptosis over necrosis, enhancing the anti-tumor efficacy of DOX. This was supported by increased reactive oxygen species production, upregulation of pro-apoptotic genes, downregulation of anti-apoptotic genes, and elevated caspase 3 and 7 activity, collectively promoting apoptosis. These findings underscore the potential of DOX-BSA-NPs as a superior alternative for targeted and controlled drug delivery, offering enhanced therapeutic efficacy and reduced side effects in ovarian cancer treatment.

摘要

多柔比星(DOX)是一种蒽环类药物,通常作为各种恶性肿瘤的一线治疗选择,可单独使用或与其他化疗药物联合使用。然而,其在癌症晚期的疗效需要高剂量,这会对正常细胞产生显著的细胞毒性并导致严重的副作用。纳米技术提供了一种有前景的策略,可通过控制药物释放来减轻这些缺点。在本研究中,通过去溶剂化方法合成了牛血清白蛋白纳米颗粒(BSA-NPs),并成功负载了多柔比星(DOX-BSA-NPs)。使用动态光散射、扫描电子显微镜、傅里叶变换红外光谱、紫外可见光谱和高效液相色谱进行表征,证实了药物的有效负载。体外研究表明,DOX-BSA-NPs能够实现药物的持续释放并增强细胞内递送。用DOX-BSA-NPs处理后,卵巢癌细胞的细胞毒性比游离多柔比星增加了两倍。划痕试验进一步显示癌细胞的迁移和侵袭显著减少。此外,乳酸脱氢酶(LDH)测定和膜联蛋白V-异硫氰酸荧光素(Annexin V-FITC)流式细胞术表明细胞凋亡倾向增加,而坏死减少,增强了多柔比星的抗肿瘤疗效。活性氧生成增加、促凋亡基因上调、抗凋亡基因下调以及半胱天冬酶3和7活性升高共同促进了细胞凋亡,这为上述结果提供了支持。这些发现强调了DOX-BSA-NPs作为靶向和控释药物递送的优越替代品的潜力,在卵巢癌治疗中具有增强的治疗效果和降低的副作用。

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