用于将化疗药物高效递送至实体瘤的间隙连接脂质体。
Gap Junction Liposomes for Efficient Delivery of Chemotherapeutics to Solid Tumors.
作者信息
Trementozzi Andrea N, Hufnagel Stephanie, Xu Haiyue, Hanafy Mahmoud S, Rosero Castro Felipe, Smyth Hugh D C, Cui Zhengrong, Stachowiak Jeanne C
机构信息
Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, United States.
College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
出版信息
ACS Biomater Sci Eng. 2020 Sep 14;6(9):4851-4857. doi: 10.1021/acsbiomaterials.0c01047. Epub 2020 Aug 24.
Chemotherapeutic delivery is limited by inefficient transport across cellular membranes. Here, we harness the cellular gap junction network to release therapeutic cargos directly into the cytosol. Specifically, cell-derived vesicles, termed connectosomes, contain gap junction transmembrane proteins that open a direct passageway to the cellular interior. Connectosomes were previously shown to substantially improve chemotherapeutic delivery . Here, we test connectosomes , using a murine breast tumor model. We demonstrate that connectosomes improve chemotherapeutic delivery to cellular targets within tumors by up to 16-fold, compared to conventional drug-loaded liposomes, suggesting an efficient alternative pathway for intracellular delivery.
化疗药物的递送受到跨细胞膜运输效率低下的限制。在此，我们利用细胞间隙连接网络将治疗性货物直接释放到细胞质中。具体而言，细胞衍生的囊泡，称为连接体，含有间隙连接跨膜蛋白，这些蛋白打开了一条通向细胞内部的直接通道。先前已证明连接体可显著改善化疗药物的递送。在此，我们使用小鼠乳腺肿瘤模型测试连接体。我们证明，与传统的载药脂质体相比，连接体将化疗药物递送至肿瘤内细胞靶点的效率提高了多达16倍，这表明存在一种有效的细胞内递送替代途径。
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