Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin, 300072, China.
Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, China.
Macromol Biosci. 2021 Aug;21(8):e2100042. doi: 10.1002/mabi.202100042. Epub 2021 May 5.
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.
源自非肿瘤细胞的外泌体由于其良好的生物安全性和细胞间生物活性物质的天然传递，在作为药物递送载体方面具有巨大潜力。然而，与肿瘤衍生的外泌体相比，由于其与肿瘤细胞的相互作用较弱，其有效的递释受到限制。因此，必须对外泌体进行工程化改造，以提高肿瘤细胞的内化效率。通过借鉴脂质在肿瘤外泌体与肿瘤细胞相互作用中的作用，可以建立一种简单有效的策略，通过工程化外泌体膜脂质来增强肿瘤细胞的摄取。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衍生的外泌体 (Exos) 的膜脂层中，构建 PC 工程化外泌体 (PC-Exos)。结果表明，与天然 Exos 相比，PC-Exos 显著增强了肿瘤细胞的内化和摄取率，最高可达两倍。在负载治疗剂后，PC-Exos 可显著促进癌细胞内药物或 RNA 的积累，从而表现出增强的体外抗肿瘤活性。这项工作证明了工程化外泌体脂质在调节肿瘤细胞摄取中的关键作用，这可能为高效外泌体为基础的药物递送载体的设计提供思路。
