Related Experiment Video
Updated: Aug 14, 2026

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
The role of multivalent cations in oligonucleotide cellular uptake
1Department of Pharmacy and Pharmaceutics, Virginia Commonwealth University, Richmond 23298, USA.
Abstract:
Oligodeoxynucleotides (ONs) are a powerful new class of drugs whose transport to the cytoplasm or nucleus inefficient and incompletely defined. Thus, to further extend our understanding of the mechanism of ON cellular uptake, the role of multivalent cations in ON cellular uptake was examined. All the multivalent cations tested, except magnesium, significantly increase ON uptake and was predictably related to the cation's electronegativity but only partially due to an increase in surface-binding. In addition, the primary mechanism of uptake is largely independent of trypsin-sensitive surface components, cellular energy, and several specific, calcium-dependent cellular processes. Therefore, ON cellular uptake may involve an interaction between multivalent cations and either the ON, the cell membrane, or both.
Insights
Multivalent cations significantly enhance oligodeoxynucleotide (ONs) cellular uptake, independent of cellular energy or surface components. This suggests cation interactions with ONs or cell membranes drive cellular delivery.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Delivery
Background:
- Oligodeoxynucleotides (ONs) represent a promising drug class.
- Efficient cellular transport of ONs to the cytoplasm or nucleus remains a challenge.
- Understanding ON cellular uptake mechanisms is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role of multivalent cations in enhancing ON cellular uptake.
- To elucidate the mechanisms underlying cation-mediated ON cellular delivery.
Main Methods:
- Examined the effect of various multivalent cations on ON cellular uptake.
- Assessed the correlation between cation electronegativity and uptake enhancement.
- Investigated the dependence of uptake on surface components, cellular energy, and calcium-dependent processes.
Main Results:
- Most tested multivalent cations significantly increased ON uptake.
- Uptake enhancement correlated with cation electronegativity.
- The primary uptake mechanism was largely independent of trypsin-sensitive surface components, cellular energy, and specific calcium-dependent processes.
Conclusions:
- Multivalent cations play a significant role in promoting ON cellular uptake.
- The mechanism of uptake appears to involve interactions between cations and ONs or cell membranes.
- Further research is needed to fully define the cation-mediated ON cellular uptake pathway.
Related Concept Videos
Nuclear Protein Sorting
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
EDTA: Chemistry and Properties
Extraction: Advanced Methods
Complexometric Titration: Ligands
Pore Transport and Ion-Pair Transport
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
Facilitated Diffusion
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...

