Self-Adaptive Antibiofilm Effect and Immune Regulation by Hollow Cu₂MoS₄ Nanospheres for Treatment of Implant Infections

Abstract

Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow Cu 2 MoS 4 nanospheres (H-CMS NSs) with pH-responsive enzymelike activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/ peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.

Stimuli-responsive nanozymes for biomedical applications

“…Low pH and high ROS levels are major characteristics of the inflammatory microenvironment, and are utilized as triggers for stimuli-responsive nanozymes. 84,100–106 As mentioned earlier, Choi et al encapsulated dMn 3 O 4 NPs inside ROS-sensitive micelles to treat acute kidney injury. 84 The dMn 3 O 4 NPs act as CAT mimics and will be specifically released at the inflammatory site in order to scavenge the overexpressed ROS efficiently, resulting in the effective amelioration of inflammation.…”

“…In addition to the responsive release of nanozymes at inflammation sites, specific nanozymes with pH-switchable activities were proposed for anti-inflammatory therapy. 105,106 Yang et al innovatively fabricated self-adaptive hollow Cu 2 MoS 4 nanospheres (H-CMS NSs) for implant infection treatment. 105 H-CMSs exhibited POD-like and OXD-like activities in an acidic microenvironment, generating toxic radicals for bacteria killing and biofilm elimination.…”

“…105,106 Yang et al innovatively fabricated self-adaptive hollow Cu 2 MoS 4 nanospheres (H-CMS NSs) for implant infection treatment. 105 H-CMSs exhibited POD-like and OXD-like activities in an acidic microenvironment, generating toxic radicals for bacteria killing and biofilm elimination. After eradicating the infection, the microenvironment turns from acidic to neutral.…”

Self-Assembled Nanoflowers Realizes Synergistic Sterilization with Photothermal and Chemical Kinetics Therapy

“…As a result, researches have focused on nanoparticles (NPs) known as nanoenzymes, which have catalytic properties comparable to those of natural proteases. − Metal and metal oxides, in particular, are especially promising for biomedical applications due to their superior catalytic capabilities and innate antibacterial activity. − For example, Wang et al investigated the effect of ultrasmall Au/Pt NCs@GO X clusterzyme on enhancing cascade catalyzed antibiofilm resistance . Yang et al found that hollow Cu 2 MoS 4 nanospheres could be used to treat implant infections and achieve immuomodulation . The pH-responsive enzyme-like activity nanospheres (H-CMS NSs) could be used for adaptive elimination of biofilms in implant infections and for the modulation of macrophage inflammation.…”

Reactive oxygen species-mediated CuRuOX@HA hybrid nanozymes for multidrug-resistant bacterial infections with synergistic photothermal therapy

“…Moreover, some typical Cu-nanozymes such as CuO X , CuS X , Cu 2 MoS 4 , and Cu 2 WS 4 have a better catalytic capacity than that of single Cu nanozymes, and extensive research suggested that they can be used as candidates for cancer therapy and bacterial infection treatment. 26–29 However, the limited catalytic capacity of typical Cu-nanozymes is not sufficient to achieve satisfactory results.…”