Enzyme-Responsive Sugar Methacrylate-Based Nanoparticles Synthesized by RAFT-PISA

Sugar-based enzyme-responsive amphiphilic nanoparticles poly(d-gluconamidoethyl methacrylate)-block-poly(2-hydroxypropyl methacrylate) (PGAMA-b-PHPMA) were synthesized by extending poly(d-gluconamidoethyl methacrylate) macro-chain transfer agent (PGAMA macro-CTA) with 2-hydroxypropyl methacrylate (HPMA) via Reversible Addition–Fragmentation chain Transfer mediated by Polymerization-Induced Self-Assembly. By varying the degree of polymerization from 100 to 400 and solids content from 10 to 20 wt %, a range of controllable morphologies was achieved. Additionally, these sugar-based amphiphilic nanoparticles exhibited good colloidal stability in neutral and slightly acidic aqueous solutions. Notably, the enzymatic response of these nanoparticles was demonstrated using Dynamic Light Scattering, Transmission Electron Microscopy, Zeta potential measurements, Size Exclusion Chromatography, and 1H NMR spectroscopy. By comparing the obtained PGAMA-b-PHPMA nanoparticles before and after enzymatic hydrolysis, significant changes in size and morphology together with a decrease in surface charge from 30.7 to 0.4 mV were observed, clearly indicating their responsiveness to enzymatic activity. This methodology provides a facile and efficient route to obtain nanoparticles with controlled morphology, high stability, and enzymatic responsiveness.