Multi-responsive protein nanocarriers from an anionic dynamic covalent copolymer
文献情報
Xiaobei Wang, Lin Wang, Shixia Yang, Hanying Zhao
On the basis of an active ester monomer methacryloylacetone oxime (MAO), a well-defined hydrazide-containing block copolymer poly(poly(ethylene glycol methacrylate))-b-poly(methylacryloylhydrazide) (P(PEGMA)-b-PMAH) was synthesized by RAFT polymerization and subsequent aminolysis in the presence of hydrazine hydrate. The dynamic covalent copolymer was generated by the bioconjugation of pyridoxal phosphate (PLP) to the pendant hydrazide groups through reversible acylhydrazone linkages. An in vitro study confirmed that the block copolymer and the PLP-conjugated dynamer were nontoxic to HeLa cells. The PLP-conjugated dynamer was negatively charged at physiological pH. Polyion complex (PIC) micelles were formed through electrostatic interaction between lysozyme and the PLP-conjugated dynamer. These PIC micelles demonstrated pH-, salt-, and enzyme-responsive features. The enzymatic activity of PIC micelles toward the hydrolysis of the bacterial substrate Micrococcus luteus cells was evaluated. A reduced activity was observed after lysozyme was entrapped in the PIC micelles because of the shielding effect of the P(PEGMA) corona. However, the dissociation of micelles, triggered by the increase in ionic strength of the milieu, led to the recovery of lysozyme activity. These PIC micelles formed by the PLP-conjugated dynamer and protein have potential applications in biomedical and bioengineering areas.
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