Surface-Active Plasma-Polymerized Nanoparticles for Multifunctional Diagnostic, Targeting, and Therapeutic Probes

Abstract

Surface-functionalized polymeric nanoparticles have advanced the field of nanomedicine as promising constructs for targeted delivery of molecular cargo as well as diagnostics and therapeutics. Conventionally, the functionalization of polymeric nanoparticles incorporates tedious wet chemical methods that require complex, multistep protocols. Surface-active plasma-polymerized nanoparticles (PPNs) produced by a dry, low-pressure plasma process can be easily functionalized with multiple ligands in a simple step. However, plasma polymerization remains limited by the challenge of efficient collection of PPNs from low-pressure plasma reactors. Here, we demonstrate a simple method to overcome this limitation by delaying the inflow of the polymer-forming precursor gas, acetylene, into a nitrogen and argon plasma discharge. We provide evidence that this cutting-edge development in the plasma polymerization method drastically enhances the collection yield of nanoparticles by 2.5-fold, compared to the simultaneous inflow of the gases. COMSOL Multiphysics simulations support our experimental data and provide insights into the role of pressure gradients in regulating the forces controlling the collection of the particles. Surface characterization data revealed that changing the sequence of the precursor gas inflow had no significant effect on the physicochemical properties of the nanoparticles, as critically important for theranostic applications. A model, green fluorescent protein, was successfully conjugated to the surface of the PPNs via a reagent-free, one-step incubation process that immobilized the biomolecule while retaining its biological activity. Cytotoxicity of the particles was assessed by a lactate dehydrogenase (LDH) assay at concentrations of up to 5 × 105 nanoparticles per cell. Despite their high concentrations, the nanoparticles were remarkably well tolerated by the cells, demonstrating their superb potential for in vivo cellular uptake. This study advances previous research on plasma-polymerized nanoparticles, introducing a low-waste synthesis method that achieves higher yields. This sustainable technology has important implications for the production of multifunctional nanoparticles for drug delivery, tumor targeting, and medical imaging.