Chemotherapeutic Drug‐Conjugated Microbeads Demonstrate Preferential Binding to Methylated Plasmid DNA

Abstract

Plasmid DNA (pDNA) is an attractive therapeutic biomolecule in several diseases including cancer, AIDS, cystic fibrosis, Parkinson's disease, and Alzheimer's disease. Increasing demand for plasmid DNA as a therapeutic biomolecule for transgene expression or vaccine applications necessitate novel approaches to bioprocessing. The synthesis, characterization and evaluation of aminoglycoside-derived hydrogel microbeads (Amikabeads) for pDNA binding is described previously. Here, the generation and evaluation of novel chemotherapeutic drug-conjugated microbeads for application in pDNA binding and recovery is described. Chemotherapeutic drug-conjugated Amikabeads demonstrate higher binding of methylated pDNA compared to unmethylated pDNA in presence of high salt concentrations. Desorption of plasmids from drug-conjugated microbeads is facilitated by the use of organic modifiers. The observed differences in binding methylated versus unmethylated DNA can make drug-conjugated microbeads useful in diagnostic as well as therapeutic applications. These results demonstrate that anti-cancer drugs represent a diverse set of ligands that may be exploited for molecular engineering of novel DNA binding materials for applications in delivery, diagnostics, and biomanufacturing.

Intelligent DNA-Based Hydrogels for Bioanalysis and Therapeutics

“…In order to solve these problems, researchers devote themselves to the study of drugs. In material-controlled release systems, including cell membranes, nanomaterials, liposomes and hydrogels, etc., these drug delivery systems can control drug release in cells or tissues in time and space by improving the efficiency of drug treatment, and reducing side effects and dosage to achieve the purpose of increasing treatment. − Due to their special physical and chemical properties and good plasticity, hydrogels can be made into different sizes to suit various drug delivery routes. The cross-linked network structure in the hydrogel prevents the intrusion of various proteins and prevents the drug molecules from being degraded by the enzymes that invade the hydrogel, thus maintaining biological activity.…”