Well‐defined succinylated chitosan‐O‐poly(oligo(ethylene glycol)methacrylate) for pH‐reversible shielding of cationic nanocarriers

A novel type of well‐defined graft copolymer, succinylated chitosan‐O‐poly(oligo(ethylene glycol)methacrylate) (SC‐POEGMA), was developed for pH‐reversible poly(ethylene glyocol) (PEG) shielding of cationic nanocarriers. Chitosan‐O‐POEGMA (CS‐POEGMA) was first synthesized via single electron transfer‐living radical polymerization of oligo(ethylene glyol) methacrylate (OEGMA) using O‐brominated chitosan (CS‐Br) as a macromolecular initiator and Cu(I)Br/1,1,4,7,10,10‐hexamethyltriethylenetetramine as a catalyst. The subsequent succinylation of the chitosan backbone gave the titled copolymers. The content of POEGMA in CS‐POEGMA could be widely modulated by varying the degree of bromination and feed ratio of OEGMA to CS‐Br, without compromising the amino density of chitosan backbone. The hierarchical assembly between SC‐POEGMA and trimethylated chitosan‐O‐poly(ε‐caprolactone) (TMC‐PCL) micelles was further studied. At pH 7.4, the stoichiometric interactions between SC and TMC segments to form polyampholyte–polyelectrolyte complexes led to the formation of PEG‐shielded micelles. The hierarchially assembled micelles could be disassembled into the pristine TMC‐PCL micelles, when the medium pH was below a certain pH (pHφ). By varying the degree of succinylation of SC‐POEGMA, the pHφ value could be facilely modulated from 6.5 to 3.5 to meet the needs for specific biomedical applications.