Synthesis and Multi-Responsive Self-Assembly of Cationic Poly(caprolactone)-Poly(ethylene glycol) Multiblock Copolymers

Individual dissimilar blocks were combined to obtain well-defined A(n)B(n) and (A-B-A)(n) types of cationic amphiphilic multiblock copolymers (MBCs) through mild sequential nucleophilic substitution without formation of byproducts. MBCs were synthesized by reacting end-functional polymer blocks of poly(caprolactone) (PCL), poly(ethylene glycol) (PEG), and PCL-b-PEG-b-PCL. For selective degradation, acid-and base-labile ester as well as reducible disulfide groups were introduced as linkers between the blocks. The micellar self-assemblies of these MBCs showed exceptional stability under normal physiological conditions with negligible release of the guest molecules. Selective disassembly under mildly acidic and basic conditions or in the presence of reducing agents caused triggered release of the guest molecules. This strategy is versatile and opens an opportunity to obtain a variety of tailor-made MBCs for selective and triggered release of therapeutics.