Enhancing pDNA Delivery with Hydroquinine Polymers by Modulating Structure and Composition

Quinine is a promising natural product building block for polymer-based nucleic acid delivery vehicles as its structure enables DNA binding through both intercalation and electrostatic interactions. However, studies exploring the potential of quinine-based polymers applications (transfection) are limited. In this work, we used hydroquinine-functionalized monomer, HQ, with 2-hydroxyethyl acrylate to create family seven (HQ-X, X = mole percentage HQ), percentages HQ ranging from 12 100%. We developed flow cytometer-based assay studying polymer–pDNA complexes (polyplex particles) directly demonstrate that polymer composition monomer influence polyplex characteristics such pDNA loading extent adsorption serum proteins on particles. Biological experiments revealed maximum transgene expression, outperforming commercial controls, was achieved HQ-25 HQ-35 these two variants sustained gene expression over 96 h. HQ-44, HQ-60, HQ-100 were not successful in inducing despite being able deliver into cells, highlighting release likely bottleneck transfection higher content. Using confocal imaging, quantified colocalization between lysosomes, proving remarkable endosomal escape capabilities HQ-X polymers. Overall, study demonstrates advantages well provides guiding principles improving composition, supporting development next generation harnessing power products.