Radical Retention and Functional Stability of Plasma‐Polymerized Nanoparticles for Long‐Term Biofunctionalization

Abstract Plasma polymerization enables rapid, solvent‐free synthesis of polymeric nanoparticles (PPNs) bearing long‐lived reactive radicals, which create a highly functionalized interface enabling single‐step covalent attachment of diverse molecules. A major barrier to translation, however, is the limited understanding of how storage conditions affect physicochemical stability and functionality. Here, it is demonstrated that PPNs retain exceptional physicochemical stability while retaining their functionality as nanocarrier when stored under optimized conditions. Dry‐phase storage at ambient temperature maintained a stable hydrodynamic size (207 ± 3.1 nm) and preserved 62.0 ± 2.0% of the initial radical concentration over 12 weeks, with no measurable changes in elemental composition or chemical bonding, confirmed by dynamic light scattering (DLS), electron paramagnetic resonance (EPR) spectroscopy, and X‐ray photoelectron spectroscopy (XPS). Even after one year of storage, aged PPNs exhibited equivalent interfacial reactivity to freshly prepared particles, evidenced by efficient covalent conjugation with Nile Blue, highlighted through fluorescence spectroscopy, attenuated total reflectance – Fourier transform infrared spectroscopy (ATR‐FTIR), and XPS. Intracellular uptake studies revealed that functionalized PPNs with aged cores retained bioactivity, exhibiting internalization in A549 lung cancer cells comparable to freshly synthesized counterparts. These findings establish key parameters for preserving PPN surface reactivity and biofunctionality, offering important design guidelines for long‐term storage.