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由天然蛋黄脂质组装的纳米载体用于治疗药物的肿瘤靶向递送。

Nanovector Assembled from Natural Egg Yolk Lipids for Tumor-Targeted Delivery of Therapeutics.

机构信息

Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital , Nanjing Medical University , Huai'an 223300 , China.

Department of Clinical Oncology, The Affiliated Huaian No.1 People's Hospital , Nanjing Medical University , Huai'an 223300 , China.

出版信息

ACS Appl Mater Interfaces. 2020 Feb 19;12(7):7984-7994. doi: 10.1021/acsami.9b22293. Epub 2020 Feb 5.

Abstract

Nanomedicine uses nanotechnology-based strategies for precision tumor therapy, including passive and ligand-mediated active tumor targeting by nanocarriers. However, the possible biotoxicity of chemosynthetic nanovectors limits their clinical applications. A novel natural egg yolk lipid nanovector (EYLN) was developed for effective loading and delivery of therapeutic agents. Lipids were extracted from egg yolks and reassembled into nanosized particles. EYLNs' stability, cellular uptake, toxicity, and delivery capacity for therapeutic agents were evaluated in vitro. The systemic toxicity and biodistribution of EYLNs were analyzed in normal mice, and the therapeutic effects of doxorubicin (Dox)-loaded EYLNs were evaluated in mouse breast cancer and hepatoma models. EYLNs had a particle size of ∼40 nm and a surface ζ-potential of -45 mV and were effectively internalized by tumor cells, without showing toxicity and side effects in vitro and in vivo. Importantly, their excellent permeability and retention effect significantly enhanced the distribution of EYLNs at tumor sites, and EYLN-Dox effectively inhibited the tumor growth in both mouse models. Targeted modification with folic acid further promoted vector-mediated drug distribution in tumors. This study demonstrates that lipids with specific proportions in the egg yolk can be used to construct natural drug vectors, providing a new strategy for nano-oncology research.

摘要

纳米医学利用基于纳米技术的策略进行精准肿瘤治疗,包括通过纳米载体进行被动和配体介导的主动肿瘤靶向。然而,化学合成纳米载体的潜在生物毒性限制了其临床应用。本研究开发了一种新型天然蛋黄脂质纳米载体(EYLN),用于有效负载和递送达药物。从蛋黄中提取脂质并重新组装成纳米大小的颗粒。体外评估了 EYLNs 的稳定性、细胞摄取、毒性和治疗剂的递送能力。在正常小鼠中分析了 EYLNs 的全身毒性和生物分布,并在小鼠乳腺癌和肝癌模型中评估了载多柔比星(Dox)的 EYLNs 的治疗效果。EYLN 的粒径约为 40nm,表面 ζ 电位为-45mV,可有效被肿瘤细胞内化,在体外和体内均无毒性和副作用。重要的是,其优异的通透性和滞留效应显著增强了 EYLNs 在肿瘤部位的分布,EYLN-Dox 有效抑制了两种小鼠模型中的肿瘤生长。通过叶酸进行靶向修饰进一步促进了载体介导的药物在肿瘤中的分布。本研究表明,蛋黄中具有特定比例的脂质可用于构建天然药物载体,为纳米肿瘤学研究提供了新策略。

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