The presence of bacterial persisters is a key factor contributing to chronic infection. However, no effective treatment methods are currently available. Thus, a platform is developed, called reactive oxygen species (ROS) bomb, based on microenvironment-adaptive hydrogel microspheres, to oxidize the cell membranes of persisters in chronic periprosthetic joint infection (PJI). Fenton reagent hydroxy iron oxide (FeOOH) and a glucose oxidase (GOx)/calcium phosphate (CaP) acid-responsive shell are sequentially induced on the surface of mesoporous polydopamine (PDA) nanoparticles by the PDA-mediated ion precipitation and interfacial adhesion, followed by the coloaded with glucose into microfluidic hyaluronic acid hydrogel microspheres. Hydroxyl radicals are explosively generated through GOx-mediated glucose oxidase, H 2 O 2 production, and its Fenton-like reactions with FeOOH, which also benefit from the weakly acidic microenvironment around persisters, result in the destruction of bacterial cell membrane, and subsequent overflow of cellular contents such as dsDNA, proteins, and K + . The bactericidal rates of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis persisters are up to 99.14% and 98.96%, and the bacterial loads in lesion location are significantly decreased after ROS bombs treated, effectively alleviated the inflammation and bone resorption damage. This work provides a new strategy toward persisters clearance and shows great application potential in other chronic infection-related diseases.
The fast conversion of hydrogen peroxide (H 2 O 2 ) into reactive oxygen species (ROS) at tumor sites is a promising anticancer strategy by manipulating nanomedicines with near-infrared light in the second region (NIR-II). However, this strategy is greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of nanomedicines. This dilemma mainly stems from the lack of an effective synthesis method to support high-density copper-based nanocatalysts on the surface of photothermal nanomaterials. Herein, a multifunctional nanoplatform (MCPQZ) with high–density cuprous (Cu 2 O) supported molybdenum disulfide (MoS 2 ) nanoflowers (MC NFs) is developed for the efficient killing of tumors via a potent ROS storm by an innovative method. Under NIR-II light irradiation, the ROS intensity and maximum reaction velocity ( V max ) produced by MC NFs are 21.6 and 33.8 times that of the non–irradiation group in vitro, which is much higher than most current nanomedicines. Moreover, the strong ROS storm in cancer cells is efficiently formed by MCPQZ (increased by 27.8 times compared to the control), thanks to the fact that MCPQZ effectively pre–weakens the multiple antioxidant systems of cancer cells. This work provides a novel insight to solve the bottleneck of ROS-based cancer therapy.
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