Zn-crosslinking of copolymer-bearing imidazole pendants to form polymeric nanoparticles for pH-sensitive drug delivery†

Polymers can be assembled into nanomaterials with different structures. Exploring new assembly methods for hydrophilic polymers in drug delivery is of significant importance. In this work, we further advanced this field by synthesizing novel polymeric nanoparticles via a Zn coordination-induced assembly mechanism. A new hydrophilic copolymer (polyethylene glycol-block-polyacrylic acid-modified-N-(3-aminopropyl)-imidazole (CH₃O-PEG2000-b-PAA₆₀-Imi)) was designed by efficiently coupling imidazole pendants onto the PAA chain within CH₃O-PEG2000-b-PAA₆₀. The coordination between the imidazole pendants and zinc ions induced the crosslinking of the resulting copolymers into polymeric nanoparticles (CH₃O-PEG2000-b-PAA₆₀-(Imi/Zn)). Exposure of the polymeric nanoparticles to slightly acidic conditions disrupted the coordination bond between the imidazole pendants and the zinc ions. The pH-responsive property led to the disintegration of the polymerized nanoparticles and the release of the drug. In vitro results further confirmed that the drug-loaded CH₃O-PEG2000-b-PAA₆₀-(Imi/Zn) exhibited toxicity to tumor cells. Accordingly, the coordination-induced assembly mechanism shows great promise for fabricating polymeric nanoparticles, particularly when the use of water as a solvent is essential.