PUBLICATION
Intracellular delivery and deep tissue penetration of nucleoside triphosphates using photocleavable covalently bound dendritic polycations
- Authors
- Ma, J., Wehrle, J., Frank, D., Lorenzen, L., Popp, C., Driever, W., Grosse, R., Jessen, H.J.
- ID
- ZDB-PUB-240503-16
- Date
- 2024
- Source
- Chemical science 15: 647864876478-6487 (Journal)
- Registered Authors
- Driever, Wolfgang
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 38699261 Full text @ Chem Sci
Citation
Ma, J., Wehrle, J., Frank, D., Lorenzen, L., Popp, C., Driever, W., Grosse, R., Jessen, H.J. (2024) Intracellular delivery and deep tissue penetration of nucleoside triphosphates using photocleavable covalently bound dendritic polycations. Chemical science. 15:647864876478-6487.
Abstract
Nucleoside triphosphates (NTPs) are essential in various biological processes. Cellular or even organismal controlled delivery of NTPs would be highly desirable, yet in cellulo and in vivo applications are hampered owing to their negative charge leading to cell impermeability. NTP transporters or NTP prodrugs have been developed, but a spatial and temporal control of the release of the investigated molecules remains challenging with these strategies. Herein, we describe a general approach to enable intracellular delivery of NTPs using covalently bound dendritic polycations, which are derived from PAMAM dendrons and their guanidinium derivatives. By design, these modifications are fully removable through attachment on a photocage, ready to deliver the native NTP upon irradiation enabling spatiotemporal control over nucleotide release. We study the intracellular distribution of the compounds depending on the linker and dendron generation as well as side chain modifications. Importantly, as the polycation is bound covalently, these molecules can also penetrate deeply into the tissue of living organisms, such as zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping