The Library
Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery
Tools
Tools
Tools
Tan, Angel, Liu, Qingtao, Septiadi, Dedy, Chu, Shuiling, Liu, Tianqing, Richards, Sarah-Jane, Rothen-Rutishauser, Barbara, Petri-Fink, Alke, Gibson, Matthew I. and Boyd, Ben J. (2021) Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery. Journal of Materials Chemistry B, 9 (26). pp. 5365-5373. doi:10.1039/D1TB00721A ISSN 2050-750X.
|
PDF
WRAP-Understanding-selectivity-metabolic-click-targeting-multicellular-environments-tissue-2021.pdf - Accepted Version - Requires a PDF viewer. Download (2369Kb) | Preview |
Official URL: http://dx.doi.org/10.1039/D1TB00721A
Abstract
Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-D-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO–glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.
| Item Type: | Journal Article | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QP Physiology R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology |
||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Metabolism, Multicellularity, Tissues, Cancer cells, Drugs | ||||||||||||||||||
| Journal or Publication Title: | Journal of Materials Chemistry B | ||||||||||||||||||
| Publisher: | R S C Publications | ||||||||||||||||||
| ISSN: | 2050-750X | ||||||||||||||||||
| Official Date: | 14 July 2021 | ||||||||||||||||||
| Dates: |
|
||||||||||||||||||
| Volume: | 9 | ||||||||||||||||||
| Number: | 26 | ||||||||||||||||||
| Page Range: | pp. 5365-5373 | ||||||||||||||||||
| DOI: | 10.1039/D1TB00721A | ||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||||||||
| Date of first compliant deposit: | 24 June 2021 | ||||||||||||||||||
| Date of first compliant Open Access: | 22 June 2022 | ||||||||||||||||||
| RIOXX Funder/Project Grant: |
|
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
