Self-immolative Amphiphilic Diblock Copolymers with Individually Triggerable Blocks.

Self-immolative polymers are a growing class of degradable polymers that undergo end-to-end depolymerization after the stimuli-responsive cleavage of an end-cap or backbone unit. Their incorporation into amphiphilic block copolymers can lead to functions such as the disintegration of copolymer nanoassemblies when depolymerization is triggered. However, diblock copolymers have not yet been developed where both blocks are self-immolative. Described here is the synthesis, self-assembly, and triggered depolymerization of self-immolative block copolymers with individually triggerable hydrophilic and hydrophobic blocks. Neutral and cationic hydrophilic polyglyxoylamides (PGAm) with acid-responsive end caps were synthesized and coupled to an ultraviolet (UV) light-triggerable poly(ethyl glyoxylate) (PEtG) hydrophobic block. The resulting block copolymers self-assembled to form nanoparticles in aqueous solution, and their depolymerization in response to acid and UV light was studied by techniques including light scattering, NMR spectroscopy, and electron microscopy. Acid led to selective depolymerization of the PGAm blocks, leading to aggregation, while UV light led to selective depolymerization of the PEtG block, leading to disassembly. This self-immolative block copolymer system provides an enhanced level of control over smart copolymer assemblies and their degradation.