Fabrication of single-chain polymer nanoparticles by light-induced inverse electron demand diels-alder (Photo-IEDDA) reaction

Single-chain polymer nanoparticles (SCNPs) have garnered significant attention due to their ability to mimic the folding behavior of proteins and their potential in applications such as drug delivery, catalysis, and sensing. Herein, we present a novel approach for preparation of SCNPs using a photo-induced inverse electron-demand Diels-Alder (photo-IEDDA) reaction. The base polymer, P(MMA-co-HEMA), synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, was functionalized with dihydrotetrazine (dHTz) and norbornene (Nb) moieties through esterification over HEMA units. Upon irradiation of a dilute solution of the modified polymer, P(MMA-co-HEMA)-M−PPA−dHTz/Nb, in the presence of a photosensitizer, dihydrotetrazine groups were in situ converted to reactive tetrazine moieties, enabling intramolecular crosslinking via the photo-IEDDA reaction. This process yielded sub-10 nm SCNPs with high precision and control. The integration of light-triggered reactivity with efficient click chemistry highlights the potential of this method for the scalable production of well-defined SCNPs with tailored properties for advanced applications in nanotechnology and materials science.