Abstract
Nanoparticles have been used for effectively delivering imaging agents and therapeutic drugs into stem cells. However, nanoparticles are not sufficiently internalized into stem cells; thus, new delivery method of nanoparticles into stem cells is urgently needed. Herein, we develop bicyclo[6.1.0]nonyne (BCN)-conjugated gold nanoparticles (BCN-AuNPs), which can be bioorthogonally conjugated to azide (-N3) groups on the surface of metabolically engineered stem cells via bioorthogonal click chemistry. For incorporating azide groups on the cell surface, first, human adipose-derived mesenchymal stem cells (hMSCs) were metabolically engineered with N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz). Second, clickable BCN-AuNPs were bioorthogonally conjugated to azide groups on Ac4ManNAz-treated hMSCs. Importantly, a large amount of BCN-AuNPs was specifically conjugated to metabolically engineered hMSCs and then internalized rapidly into stem cells through membrane turnover mechanism, compared to the conventional nanoparticle-derived endocytosis mechanism. Furthermore, BCN-AuNPs entrapped in endosomal/lysosomal compartment could escape efficiently to the cytoplasm of metabolically engineered stem cells. Finally, BCN-AuNPs in stem cells were very safe, and they did not affect stem cell functions, such as self-renewal and differentiation capacity. These bioorthogonally conjugated nanoparticles on metabolically engineered stem cells can enhance the cellular uptake of nanoparticles via bioorthogonal conjugation mechanism.
Original language | English |
---|---|
Pages (from-to) | 199-214 |
Number of pages | 16 |
Journal | Bioconjugate Chemistry |
Volume | 32 |
Issue number | 1 |
DOIs | |
State | Published - 20 Jan 2021 |
Bibliographical note
Funding Information:This work was supported by grants from the National Research Foundation (NRF) of Korea, funded by the Ministry of Science (NRF-2019R1A2C3006283), the KU-KIST Graduate School of Converging Science and Technology (Korea University) and the Intramural Research Program of KIST.
Publisher Copyright:
© 2021 American Chemical Society.