Conformational Behaviour of Photoresponsive Single-Chain Polymeric Nanoparticles

Abstract

Inspired by nature’s dynamic materials, we here develop photoresponsive single-chain polymeric nanoparticles (SCPNs) that undergo light-induced changes in their polymeric microenvironment while retaining their global conformation. Stimuli-responsive SCPNs have been explored, but stable photoswitches that operate through solubility switching in water remain underdeveloped. We investigate water-soluble SCPNs with three different covalently attached photoswitches that are based on donor-acceptor Stenhouse adducts (DASAs), spiropyran, or the aryl azopyrazolium ionic photoswitch (AAIP). From the photophysical studies, we identify AAIP as the most robust photoswitch, displaying excellent photostability, high photostationary-state fidelity, and minimal fatigue. Using dynamic light scattering (DLS), fluorescence probes, nuclear magnetic resonance (NMR), and small angle X-ray (SAXS) studies, we elucidate how photoswitching and side-graft design affect the global SCPN conformation. SAXS reveals compact nanoparticles (RG ≈ 5-6 nm) for all AAIP functionalized polymers, and their global conformation is not affected by the E-Z photoisomerization of the AAIP grafts. In contrast, NMR and fluorescence data indicate a clear shift in microenvironment polarity upon photoisomerization. In addition, cytotoxicity assays show that the biological response is highly sensitive to subtle structural variations within these polymers. Together, these findings expand our knowledge of light-responsive SCPNs by introducing a new, stable photoswitch. Our results demonstrate that local microstructure and global conformation can be decoupled, and highlight the importance of precise polymer design for future biological applications.