期刊
CHEMMEDCHEM
卷 16, 期 1, 页码 164-178出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.202000490
关键词
cancer; cell lines; drug delivery; neuropeptide Y; shuttling
资金
- German Science Foundation Deutsche Forschungsgemeinschaft (German Research Foundation) [CRC 1052, 209933838]
- European Union (EU)
- Federal State of Saxony
- Projekt DEAL
Research shows that in the drug shuttle system of G protein-coupled receptors, a higher amount of peptide uptake can be achieved by pulsing the application of the drug, and the efficiency of recycling receptors and peptide uptake varies in different cell systems.
G protein-coupled receptors (GPCRs) can be used to shuttle peptide-drug conjugates into cells. But, for efficient therapy, a high concentration of cargo needs to be delivered. To explore this, we studied the pharmacologically interesting neuropeptide Y(1)receptor (Y1R) in one recombinant and three oncogenic cell systems that endogenously express the receptor. We demonstrate that recycled receptors behave identically to newly synthesized receptors with respect to ligand binding and internalization pathways. Depending on the cell system, biosynthesis, recycling efficiency, and peptide uptake differ partially, but shuttling was efficient in all systems. However, by comparing continuous application of the ligand for four hours to four cycles of internalization and recycling in between, a significantly higher amount of peptide uptake was achieved in the pulsed application (150-250 % to 300-400 %). Accordingly, in this well-suited drug shuttle system pulsed application is superior under all investigated conditions and should be considered for innovative, targeted drug delivery in general.
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