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.

Surface Bio‐engineered Polymeric Nanoparticles

“…[66,[101][102][103][104][105] Depositing plasmas, on the other hand, coat the surfaces of substrates with either an additional layer like plasma polymer films [106][107][108][109][110][111] and magnetronsputtered coatings [112][113][114][115][116][117] or synthesize new material such as nanoparticles. [118][119][120][121] The plasma processes share a common underlying concept: The electrons in the plasma are accelerated by electric fields, and they excite the reactant gases, resulting in ionization, radical fragmentation, and enhanced plasma phase chemistry. [107] With an organic gas such as acetylene [122] or monomer vapors such as allylamine, [123,124] acrylic acid, [125] octadiene, [126,127] or thiophene, [128,129] plasma polymerization can be used not only for the coating of particulate surfaces but also for the production of organic nanoparticles.…”

“…[107] With an organic gas such as acetylene [122] or monomer vapors such as allylamine, [123,124] acrylic acid, [125] octadiene, [126,127] or thiophene, [128,129] plasma polymerization can be used not only for the coating of particulate surfaces but also for the production of organic nanoparticles. [120,121,130] Originally known as plasma dust or powder, plasma polymerized nanoparticles (PPNs) were explored as by-products in space or contaminants in semiconductor industry plasma processes. [131] More recently, their potential as nanocarriers in the biomedical field has been realized and is being explored for multi-functional therapeutics.…”

“…[132] Plasma polymerization of nanoparticles results in radicalrich surfaces allowing the immobilization of multifunctional biomolecules in a single incubation step. [121,133] Thus, plasma polymerization presents an appealing alternative to wet chemical surface functionalization for applications in biomedicine.…”

“…These methods are receiving considerable interest for multifaceted biomaterial applications due to their scalability and versatility. [100,107,120,121,333,334] The growing research in plasma polymerized nanoparticles is projected to have pivotal implications in diagnostic and therapeutic applications. Their solvent-free fabrication using small amounts of gases and rapid polymerization rates as well as their biofunctionalization via reagent-free single-step incubations, promise large-scale industrial production, a feature critical for their efficient clinical translation.…”

“…[ 66,101–105 ] Depositing plasmas, on the other hand, coat the surfaces of substrates with either an additional layer like plasma polymer films [ 106–111 ] and magnetron‐sputtered coatings [ 112–117 ] or synthesize new material such as nanoparticles. [ 118–121 ]…”