Phosphatidylcholine-Engineered Exosomes for Enhanced Tumor Cell Uptake and Intracellular Antitumor Drug Delivery.
Phosphatidylcholine-Engineered Exosomes for Enhanced Tumor Cell Uptake and Intracellular Antitumor Drug Delivery.
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DOI：
10.1002/mabi.202100042
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发表时间：
2021-05
影响因子：
4.6
通讯作者：
Qi Zhan;Kaikai Yi;Xueping Li;Xiaoteng Cui;Eryan Yang;Ning Chen;Xubo Yuan;Jin Zhao;Xin Hou
中科院分区：
文献类型：
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作者：
Qi Zhan;Kaikai Yi;Xueping Li;Xiaoteng Cui;Eryan Yang;Ning Chen;Xubo Yuan;Jin Zhao;Xin Hou
来源于非肿瘤细胞的外泌体具有良好的生物安全性和生物活性物质在细胞间的自然转移性，因此作为药物载体具有很大的潜力。然而，与肿瘤来源的外泌体相比，有效递送受限于它们与肿瘤细胞的弱相互作用。工程化外泌体以提高肿瘤细胞内化效率是至关重要的。一个简单而有效的策略，以提高肿瘤细胞的摄取通过工程化的外泌体膜脂质，可以建立通过借鉴肿瘤外泌体与肿瘤细胞相互作用的脂质的作用。通过简单孵育将两亲性磷脂酰胆碱（PC）分子插入网织红细胞来源的外泌体（Exos）的膜脂质层中以构建PC工程化外泌体（PC-Exos）。证明了与天然Exos相比，PC-Exos显示出显著增强的肿瘤细胞内化和摄取速率，高达两倍的增加。在治疗剂负载后，PC-Exos显著促进癌细胞中的细胞内药物或RNA积累，从而显示出增强的体外抗肿瘤活性。这项工作证明了工程外泌体脂质在调节癌症细胞摄取中的关键作用，这可能有助于设计基于外泌体的高效药物递送载体。
Exosomes derived from non-tumor cells hold great potential as drug delivery vehicles because of their good biosafety and natural transference of bioactive cargo between cells. However, compared to tumor-derived exosomes, efficient delivery is limited by their weak interactions with tumor cells. It is essential to engineer exosomes that improve tumor cellular internalization efficiency. A simple and effective strategy to enhance tumor cell uptake by engineering the exosome membrane lipids can be established by drawing on the role of lipids in tumor exosomes interacting with tumor cells. Amphiphilic phosphatidylcholine (PC) molecules are inserted into the membrane lipid layer of reticulocyte-derived exosomes (Exos) by simple incubation to construct PC-engineered exosomes (PC-Exos). It is demonstrated that PC-Exos showed significantly enhanced tumor cell internalization and uptake rate compared to native Exos, up to a twofold increase. After therapeutic agent loading, PC-Exos remarkably promotes intracellular drug or RNA accumulation in cancer cells, thus showing enhanced in vitro anti-tumor activity. This work demonstrates the crucial role of engineering exosomal lipids in modulating cancer cellular uptake, which may shed light on the design of high-efficiency exosome-based drug delivery carriers.