Enhancing Gene Delivery and Immune Modulation in Primary Dendritic Cells by Utilizing Composites of Iron Oxide Nanocubes and Biocompatible PLGA–PDMAEMA Polymers

High Resolution Image Download MS PowerPoint Slide Dendritic cells (DCs) represent pivotal targets in immunotherapy, gene therapy, and vaccine delivery for major diseases including cancer, autoimmune diseases, and transplant rejection. Overcoming the challenge of efficient gene delivery via conventional nonviral molecules into primary DCs has been a persistent obstacle. Within this research, we introduce an innovative gene delivery system utilizing magnetic iron oxide nanocubes (MCs) encapsulated with a biocompatible polymer, poly(lactic- co -glycolic acid) (PL), and a cationic polymer, poly(2-(dimethylamino)ethyl methacrylate) (PD), facilitated by a magnetic field. Positively charged MC–PL–PD and MC–PL–PD/PD (double coating of PD) composites were synthesized, and plasmid DNA (pMAX-GFP) attachment ensued. The nanocomposite with double layers coated with PD displayed increased positive charge despite the incorporation of plasmid DNA. In addition, these nanocomposites exhibited superparamagnetic properties with a saturation magnetization of 4.5 emu/g. At concentrations ranging from 25 to 100 μg/mL, the nanocomposites demonstrated minimal toxicity on bone marrow-derived dendritic cells (BMDCs) and exhibited efficient cellular uptake under the influence of a magnetic field. Composites with higher positive charges and increased amounts demonstrated enhanced plasmid transfection efficiency without activating BMDCs. These findings suggest that using MC–PL–PD and MC–PL–PD/PD nanocomposites as carriers holds promise as a viable and effective gene delivery platform to primary DCs, revealing their potential in advancing gene-based therapeutic approaches.