Heparin‐Mimicking Sulfonated Polymer Nanoparticles via RAFT Polymerization‐Induced Self‐Assembly

Heparin plays a significant role in wound healing and tissue regeneration applications, through stabilization of fibroblast growth factors (FGF). Risks associated with batch‐to‐batch variability and contamination from its biological sources have led to the development of synthetic, highly sulfonated polymers as promising heparin mimics. In this work, a systematic study of an aqueous polymerization‐induced self‐assembly (PISA) of styrene from poly(2‐acrylamido‐2‐methylpropane sodium sulfonate) (P(AMPS)) macro reversible addition–fragmentation chain transfer (macro‐RAFT) agents produced a variety of spherical heparin‐mimicking nanoparticles, which were further characterized with light scattering and electron microscopy techniques. None of the nanoparticles tested showed toxicity against mammalian cells; however, significant hemolytic activity was observed. Nonetheless, the heparin‐mimicking nanoparticles outperformed both heparin and linear P(AMPS) in cellular proliferation assays, suggesting increased bFGF stabilization efficiencies, possibly due to the high density of sulfonated moieties at the particle surface. Synthesis of well‐defined, heparin‐mimicking nanoparticles via a facile polymerization‐induced self‐assembly (PISA) approach using heparin‐like sulfonated polymeric stabilizers is presented. The multivalent expression of these polymers yields significantly higher performance in the stabilization of the basic fibroblast growth factor, a process imperative in many biological applications.