Journal
MACROMOLECULAR BIOSCIENCE
Volume 21, Issue 8, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.202100042
Keywords
exosomes; intracellular drug delivery; membrane engineering; phosphatidylcholine; tumor cell uptake
Funding
- National Natural Science Foundation of China (NSFC) [51673146, 51673144, 81772667]
- Natural Science Foundation of Tianjin City [18JCYBJC18300, 17JCYBJC17500]
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This study demonstrated the importance of engineering exosomal lipids to enhance cancer cellular uptake, leading to improved tumor cell internalization and increased anti-tumor activity in vitro.
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.
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