Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems: a Cost-Effective Alternative

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作者
Wei Jiang Goh
Shui Zou
Wei Yi Ong
Federico Torta
Alvarez Fernandez Alexandra
Raymond M. Schiffelers
Gert Storm
Jiong-Wei Wang
Bertrand Czarny
Giorgia Pastorin
机构
[1] NUS Graduate School for Integrative Sciences and Engineering,
[2] Centre for Life Sciences (CeLS),undefined
[3] Department of Pharmacy,undefined
[4] National University of Singapore,undefined
[5] Department of Anatomy Yong Loo Lin School of Medicine,undefined
[6] National University Health System (NUHS),undefined
[7] Singapore Lipidomics Incubator (SLING),undefined
[8] Centre for Life Sciences (CeLS),undefined
[9] School of Materials Science & Engineering,undefined
[10] Nanyang Technological University,undefined
[11] Clinical Chemistry and Haematology,undefined
[12] University Medical Centre Utrecht,undefined
[13] Department of Surgery,undefined
[14] Yong Loo Lin School of Medicine,undefined
[15] National University of Singapore,undefined
[16] Cardiovascular Research Institute (CVRI),undefined
[17] National University Heart Centre Singapore (NUHCS) and National University Health System (NUHS),undefined
[18] Department of Pharmaceutics,undefined
[19] Utrecht Institute for Pharmaceutical Sciences,undefined
[20] Faculty of Science,undefined
[21] Utrecht University,undefined
[22] NUSNNI-NanoCore,undefined
[23] National University of Singapore,undefined
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摘要
Cell Derived Nanovesicles (CDNs) have been developed from the rapidly expanding field of exosomes, representing a class of bioinspired Drug Delivery Systems (DDS). However, translation to clinical applications is limited by the low yield and multi-step approach in isolating naturally secreted exosomes. Here, we show the first demonstration of a simple and rapid production method of CDNs using spin cups via a cell shearing approach, which offers clear advantages in terms of yield and cost-effectiveness over both traditional exosomes isolation, and also existing CDNs fabrication techniques. The CDNs obtained were of a higher protein yield and showed similarities in terms of physical characterization, protein and lipid analysis to both exosomes and CDNs previously reported in the literature. In addition, we investigated the mechanisms of cellular uptake of CDNs in vitro and their biodistribution in an in vivo mouse tumour model. Colocalization of the CDNs at the tumour site in a cancer mouse model was demonstrated, highlighting the potential for CDNs as anti-cancer strategy. Taken together, the results suggest that CDNs could provide a cost-effective alternative to exosomes as an ideal drug nanocarrier.
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