Tailoring Azlactone-Based Block Copolymers for Stimuli-Responsive Disassembly of Nanocarriers.

Stimuli-responsive nanoparticles based on a reactive block copolymers (BCPs) of poly(ethylene glycol)--poly(2-vinyl-4,4-dimethylazlactone) (PEG--PVDMA) have been fabricated for loading and controlled release of molecular cargoes. Microphase segregation of PEG--PVDMA BCPs enables the construction of well-defined nanoparticles in aqueous solutions. The azlactone groups in VDMA repeat units offer active sites for hydrophilization of the BCPs and functionalization by primary amines. The hydrophilization of PEG--PVDMA BCPs induces gradual reconstruction and dissociation of the BCP nanoparticles. Functional primary amines can be conjugated to PEG--PVDMA BCPs, yielding azobenzene- and pyridine-containing BCPs. The self-assembled nanoparticles made from the functionalized BCPs can disassemble in response to different external stimuli (e.g., addition of β-cyclodextrin and pH changes). The gradual reconstruction of functionalized PEG--PVDMA BCP nanoparticles caused by hydrolysis of residual azlactone groups provides a novel method to engineer sub-50 nm, well-dispersed, stimuli-responsive nanoparticles. These nanoparticles can incorporate molecular cargoes and release them upon external stimuli, making the azlactone-containing BCPs attractive platforms for the development of controlled delivery vehicles.