Dual pH-and thermoresponsive nano-objects with tunable morphologies and dye encapsulation prepared via aqueous emulsion PISA

Poly(triethylene glycol methyl ether methacrylate)-b-poly [2-(diisopropylamino)ethyl methacrylate] (PTEGMAb-PDPA) nano-objects, synthesized via polymerization-induced self-assembly (PISA), exhibit dual thermo-and pH-responsive behavior. The thermoresponsiveness originates from the lower critical solution temperature (LCST) of the PTEGMA block, while the pH-responsiveness arises from protonation of the PDPA block under acidic conditions. The hydrophilic PTEGMA block (degree of polymerization, DP = 120) was first synthesized to serve as a macro-chain transfer agent. This was followed by RAFT-mediated PISA emulsion polymerization of the pH-sensitive PDPA block (DP = 35-265) in aqueous solution at a solid content of 10 wt%. During polymerization, the block copolymers self-assembled in situ into diverse and tunable nanostructures, including micelles, branched worms, "jellyfish", and thick-walled vesicles. These nano-objects were thoroughly characterized using cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and small-angle X-ray scattering (SAXS). The in situ drug encapsulation capability of these dual-responsive nanoformulations was demonstrated using Nile Red (NR), a hydrophobic fluorescent model compound. Specifically, thick-walled vesicles (PTEGMA 120 -b-PDPA 265 ) successfully encapsulated NR during RAFT-PISA synthesis and released it under acidic conditions and/or at mildly elevated temperatures. These results highlight the potential of tailorable PTEGMA-b-PDPA nano-objects as "smart" nanocarriers for targeted and stimuli-responsive drug delivery applications.