Thermoresponsive Polymer Nanoparticles From Epoxidized Oleyl Methacrylate: Synthesis, Characterization, and In Vitro Evaluation

Thermoresponsive polymer nanoparticles (PNPs) were developed from epoxidized oleyl methacrylate (EOM), an olive oil–derived renewable monomer bearing reactive epoxide groups that enable post- or pre-polymerization functionalization for future drug, imaging, or targeting molecule conjugation. Neutral and cationic PNPs were synthesized by UV-initiated free-radical polymerization of N-isopropylacrylamide (NIPAM), EOM, and 2-aminoethyl methacrylamide (2-AEMA) introduced to generate cationic surface chemistry. Dynamic light scattering showed hydrodynamic diameters of 188.2 nm (neutral; PDI 0.079) and 222.4 nm (cationic; PDI 0.200), while cationic PNPs exhibited a high positive zeta potential (+38.6 ± 5.04 mV). Thermoresponsive behavior assessed by DLS revealed a sharp LCST-type transition for neutral PNPs at ~28°C–32°C, whereas cationic PNPs displayed a broader, shifted transition at ~35°C–42°C (~38°C), consistent with enhanced polymer–water interactions. In vitro, cationic PNPs reduced HCT116 colorectal cancer cell viability in a dose-dependent manner (IC₅₀ = 0.26 ± 0.02 mg/mL at 24 h) while showing no significant toxicity toward HUVECs. Scratch assays indicated inhibited HCT116 migration at 0.05–0.15 mg/mL. Hemocompatibility testing showed no detectable hemolysis up to 0.3 mg/mL and no effect on coagulation at ≤ 0.1 mg/mL, whereas ≥ 0.15 mg/mL inhibited clot formation. These results support EOM-based cationic thermoresponsive PNPs as sustainable, modular nanoplatforms for cancer-oriented biomedical applications.