TY - JOUR
T1 - Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems
T2 - A Cost-Effective Alternative
AU - Goh, Wei Jiang
AU - Zou, Shui
AU - Ong, Wei Yi
AU - Torta, Federico
AU - Alexandra, Alvarez Fernandez
AU - Schiffelers, Raymond M.
AU - Storm, Gert
AU - Wang, Jiong-Wei
AU - Czarny, Bertrand M S
AU - Pastorin, Giorgia
N1 - Funding Information:
This work was supported by the National University of Singapore (NUS), Department of Pharmacy (AcRF Tier 1 FRC grant R-148-000-213-112),Leung Kai Fook grant (R-148-000-227-720) and A-STAR-SERC grant (R-148-000-222-305). This work was also partly supported by the National University Health System collaborative grant (NUHS O-CRG 2016 Oct-23) to J.W.W. WJ. Goh gratefully acknowledges NUS Graduate School for Integrative Sciences and Engineering graduate for financial support of graduate studies. The authors would also like to thank A/P Gigi Chiu of National University of Singapore (NUS) for use of DLS equipment and Mr Sim Aik Yong for support from the Electron Microscopy Unit (Yong Loo Lin School of Medicine, NUS).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Cell delivery
KW - Nanobiotechnology
UR - http://www.scopus.com/inward/record.url?scp=85032465409&partnerID=8YFLogxK
U2 - 10.1038/s41598-017-14725-x
DO - 10.1038/s41598-017-14725-x
M3 - Article
AN - SCOPUS:85032465409
SN - 2045-2322
VL - 7
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 14322
ER -