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Gap Junction Liposomes for Efficient Delivery of Chemotherapeutics to Solid Tumors
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-08-17 , DOI: 10.1021/acsbiomaterials.0c01047
Andrea N Trementozzi 1 , Stephanie Hufnagel 2 , Haiyue Xu 2 , Mahmoud S Hanafy 2 , Felipe Rosero Castro 1 , Hugh D C Smyth 2 , Zhengrong Cui 2 , Jeanne C Stachowiak 1
Affiliation  

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 in vitro. Here, we test connectosomes in vivo, 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.

中文翻译:

用于将化疗药物有效递送至实体瘤的间隙连接脂质体

化疗递送受到跨细胞膜低效运输的限制。在这里,我们利用细胞间隙连接网络将治疗性物质直接释放到细胞质中。具体来说,细胞衍生的囊泡,称为连接体,含有间隙连接跨膜蛋白,可打开通往细胞内部的直接通道。先前已证明连接体可显着改善体外化疗药物的递送。在这里,我们使用鼠乳腺肿瘤模型在体内测试连接。我们证明,与传统的载药脂质体相比,连接体可将向肿瘤内细胞靶标的化学治疗递送提高多达 16 倍,这表明细胞内递送是一种有效的替代途径。
更新日期:2020-09-14
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