Intracellular Uptake Mechanism of Bioorthogonally Conjugated Nanoparticles on Metabolically Engineered Mesenchymal Stem Cells
- Authors
- Lim, Seungho; Kim, Woojun; Song, Sukyung; Shim, Man Kyu; Yoon, Hong Yeol; Kim, Byung-Soo; Kwon, Ick Chan; Kim, Kwangmeyung
- Issue Date
- 20-1월-2021
- Publisher
- AMER CHEMICAL SOC
- Citation
- BIOCONJUGATE CHEMISTRY, v.32, no.1, pp.199 - 214
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCONJUGATE CHEMISTRY
- Volume
- 32
- Number
- 1
- Start Page
- 199
- End Page
- 214
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/137804
- DOI
- 10.1021/acs.bioconjchem.0c00640
- ISSN
- 1043-1802
- 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 (-N-3) 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 (Ac(4)ManNAz). Second, clickable BCN-AuNPs were bioorthogonally conjugated to azide groups on Ac(4)ManNAz-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.
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