Hydroxyapatite (HA) is extensively used for implantable device coating; however, it lacks antibacterial property, leading to bacterial infection during orthopedic implantation surgery. Herein, to enhance the antibacterial activity of HA, a redox- and pH-responsive HA nanocomposite with photocatalytic activity was designed. A photosensitive heterostructure, zinc oxide/hydroxyapatite (ZnO.HA), was coated with Ag nanoparticles (AgNPs) with assisted gallic acid using the UV-irradiation method. An antibacterial enzyme, lysozyme, was then conjugated on the surface of the nanocomposite by a cleavable disulfide linker, resulting in a redox-sensitive nanoplatform. In comparison with bare HA, the designed nanocomposites as Lyso.CAGZ@HA displayed much higher antibacterial activity (> 5-fold) toward Escherichia coli (E. coli) owing to the synergistic antibacterial effects of ZnONPs, AgNPs, gallic acid, and lysozyme on the surface of the nanocomposite. However, antibacterial and antifouling effects are much more enhanced in Lyso.CAGZ@HA-treated bacteria as they were subjected to UVA irradiation. Moreover, the cellular uptake of nanocomposite and intracellular glutathione depletion enhanced in the presence of UVA light, resulting in reactive oxygen specious generation enhancement. Further, in vitro cytotoxicity experiments on mammalian cells (human foreskin fibroblast) revealed that nanocomposite has no cytotoxic effects. Hence, this study demonstrated that Lyso.CAGZ@HA could be considered as a potential therapeutic approach against bacterial infectious diseases.

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