Fibroin- Poly(N-vinylcaprolactam) hybrid nanoparticles: a thermoresponsive system for drug delivery

This study reports, for the first time, the design, synthesis, and characterization of thermoresponsive hybrid nanoparticles composed of silk fibroin (SF) and poly(N-vinylcaprolactam) (PNVCL) for controlled drug delivery. The system was produced using a grafting-from approach based on RAFT polymerization of N-vinylcaprolactam directly from the fibroin backbone. The resulting SF–PNVCL nanoparticles, with mean diameters below 200 nm, successfully integrate the biocompatibility of SF with the temperature-sensitive behavior of PNVCL. Hybrid formation and structural integrity were confirmed by FTIR, TGA, and PXRD analyses. Curcumin was used as a model hydrophobic agent and presented efficient encapsulation (EE ≈ 42%), exhibiting a temperature-triggered release profile, with markedly higher release at 40 °C compared to 25 °C. Cytotoxicity assays showed that curcumin-loaded hybrids were non-toxic to normal human fibroblasts (MRC-5), while promoting pronounced cytotoxicity in 4T1 breast cancer cells. Overall, these findings demonstrate that SF–PNVCL hybrid nanoparticles represent a promising new class of protein–polymer carriers capable of stimuli-responsive, controlled drug release, highlighting their potential for future biomedical applications.