Continuous-flow synthesis for Dual-stimuli-responsive fluorescent Star-PNIPAM for cell imaging

• Fluorescent star polymers are obtained by a high-efficiency continuous-flow synthesis method. • These polymers possess temperature- and pH-responsive capability. • Self-assembled nanoparticles by these polymers exhibit good cell viability , cell uptake, and cell imaging performance. Development of high-performance fluorescent materials is crucial for fluorescence imaging technology. Herein, well-defined fluorescent star poly-N-isopropylacrylamide (Flu-PNIPAM) was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization in a continuous-flow microreactor. A tetrafunctional RAFT agent and the functional monomer fluorescein undecylenoyl (Flu-UE) were synthesized, and then pumped into a microreactor with NIPAM monomer together for RAFT polymerization. The microreactor process parameters for the RAFT polymerization were optimized to obtain well-defined Flu-PNIPAM. The NIPAM and Flu-UE units endow Flu-PNIPAM with temperature and pH responsiveness, respectively. Transmission electron microscopy and dynamic light scattering analyses revealed that Flu-PNIPAM self-assembled into nanoparticles with uniform size in an aqueous solution at 37 °C. Moreover, Flu-PNIPAM exhibited good fluorescence and biocompatibility, rendering it highly promising for cell imaging .