Phosphatidylcholine‐Engineered Exosomes for Enhanced Tumor Cell Uptake and Intracellular Antitumor Drug Delivery

• Published in: Macromolecular bioscience Vol. 21; no. 8; pp. e2100042 - n/a
• Main Authors: Zhan, Qi, Yi, Kaikai, Li, Xueping, Cui, Xiaoteng, Yang, Eryan, Chen, Ning, Yuan, Xubo, Zhao, Jin, Hou, Xin, Kang, Chunsheng
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01-08-2021
• Subjects: Antineoplastic Agents - pharmacology; Cancer; Cell Line, Tumor; Chemical compounds; Drug delivery; Drug Delivery Systems; Drug development; Exosomes; Exosomes - metabolism; Incubation; Internalization; Intracellular; intracellular drug delivery; Lecithin; Lipids; membrane engineering; Membranes; Pharmacology; Phosphatidylcholine; Phosphatidylcholines; Reticulocytes; tumor cell uptake; Tumor cells; tumor cell uptake; intracellular drug delivery; exosomes; membrane engineering; phosphatidylcholine
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202100042

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.
A simple and flexible approach to engineer exosomes by regulating their lipid composition with phosphatidylcholine (PC) improves their tumor cell uptake efficiency, thereby achieving better intracellular delivery of therapeutic agents. This work demonstrates the effect of engineering exosome lipids to improve their tumor cell uptake, which provides a new strategy for the design of exosome‐based drug delivery carriers.