Optimizing Biocompatibility and Gene Delivery with DMAEA and DMAEAm: A Niacin-Derived Copolymer Approach.
Prosper P MapfumoLiên S ReichelThomas AndréStephanie HoeppenerLenhard K RudolphAnja TraegerPublished in: Biomacromolecules (2024)
Gene therapy is pivotal in nanomedicine, offering a versatile approach to disease treatment. This study aims to achieve an optimal balance between biocompatibility and efficacy, which is a common challenge in the field. A copolymer library is synthesized, incorporating niacin-derived monomers 2-acrylamidoethyl nicotinate (AAEN) or 2-(acryloyloxy)ethyl nicotinate (AEN) with N,N -(dimethylamino)ethyl acrylamide (DMAEAm) or hydrolysis-labile N,N -(dimethylamino)ethyl acrylate (DMAEA). Evaluation of the polymers' cytotoxicity profiles reveals that an increase in AAEN or DMAEA molar ratios correlates with improved biocompatibility. Remarkably, an increase in AAEN in both DMAEA and DMAEAm copolymers demonstrated enhanced transfection efficiencies of plasmid DNA in HEK293T cells. Additionally, the top-performing polymers demonstrate promising gene expression in challenging-to-transfect cells (THP-1 and Jurkat cells) and show no significant effect on modulating immune response induction in ex vivo treated murine monocytes. Overall, the best performing candidates exhibit an optimal balance between biocompatibility and efficacy, showcasing potential advancements in gene therapy.
Keyphrases
- gene therapy
- induced apoptosis
- gene expression
- immune response
- cell cycle arrest
- ionic liquid
- signaling pathway
- dna methylation
- dendritic cells
- tissue engineering
- cell death
- endoplasmic reticulum stress
- climate change
- toll like receptor
- single molecule
- cell free
- drug release
- circulating tumor
- pi k akt
- peripheral blood
- drug delivery
- combination therapy
- smoking cessation
- nucleic acid