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.