“…Some pH-triggered dynamic bonds, such as benzoxaboronic ester, hydrazine, and imine bonds, have been applied to designing intelligent nanocarriers with pH responsiveness. , The aromatic imine bond has advantages for constructing BCP micelles with sensitive pH-responsiveness due to its rapid cleavage upon external pH stimulation. , Moreover, there are strong hydrophobic interactions and π–π stacking from multiaromatic groups, which can significantly improve the stability of micelles against harsh physiological environment. , Zwitterionic MPC-based polymers have been proven to be highly biocompatible biomaterials (Food and Drug Administration (FDA)-approved) that can resist nonspecific protein adsorption and maintain long-time stability in plasma. − Moreover, zwitterionic poly(MPC) (PMPC) in conjugation with therapeutic proteins, such as interferon and antibodies, has demonstrated evident pharmacokinetic enhancement and epitope specificity. , By combining the advantages of aromatic imine bonds and zwitterionic polymers, well-structured BCP micelles were developed from the self-assembly of a zwitterionic block copolymer, poly(2-methacryloyloxyethyl phosphorylcholine- b -poly(di(ethylene glycol) methyl ether methacrylate- co -4-formylphenyl methacrylate) [PMPC- b -P(DEGMA- co -FPMA), BCP], which was synthesized by RAFT polymerization. As shown in Scheme , the FPMA components in BCP with reactive aldehyde groups provide a suitable capability for covalently conjugating with TPZD (containing an amine group) to give a hypoxia-activated BCP-TPZ conjugate through the formation of imine bonds.…”