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Keeping steps ahead of the bacteria in the race for more efficacious antibacterial strategies is increasingly difficult with the advent of bacterial resistance genes. Herein, we engineered copper sulfide nanoclusters (CuSx NCs) with variable sulfur defects for enhanced dual-treatment of bacterial infections by manipulating photothermal effects and Fenton-like activity. Next, by encasing CuSx NCs with a complex mixture of amino acids and short peptides derived from Luria-Bertani bacterial culture media as a protein corona, we managed to coax E. Coli to take up these CuSx NCs. As a whole, Amino-Pep-CuSx NCs was perceived as a food source and actively consumed by bacteria, enhancing their effective uptake by at least 1.5-fold greater than full length BSA protein BSA-corona CuSx NCs. Through strategically using defect-engineering, we successfully fine-tune photothermal effect and Fenton-like capacity of CuSx NCs. Increased sulfur defects lead to reduced but sufficient heat generation under solar-light irradiation and increased production of toxic hydroxyl radicals. By fine-tuning sulfur defects during synthesis, we achieve CuSx NCs with an optimal synergistic effect, significantly enhancing their bactericidal properties. These ultra-small and biodegradable CuSx NCs can rapidly break down after treatment for clearance. Thus, Amino-Pep-CuSx NCs demonstrate effective eradication of bacteria both in vitro and in vivo because of their relatively high uptake, optimal balanced photothermal and chemodynamic outcomes. Our study offers a straightforward and efficient method to enhance bacterial uptake of next generation of antibacterial agents.

The use of magneto-mechanical force to kill cancer cells has attracted significant attention in recent years. However, many reports have focused on in vitro experiments with a single treatment. Herein, CaO2-coated Fe3O4 core—shell magnetic nanoenzymes (Fe3O4/CaO2) are developed for low frequency vibrating magnetic field (VMF)-induced multimodal cancer therapy. Fe3O4/CaO2 are shown to efficiently generate O2, H2O2, and ·OH through hydrolysis of CaO2 and a CaO2-strengthened Fenton reaction, killing laryngeal carcinoma cells and inhibiting mouse tumor growth (chemodynamic therapy (CDT)). Both Fe3O4 and Fe3O4/CaO2 triggered by a VMF are shown to damage the cytoskeleton of cancer cells through magneto-mechanical force (maxima: 223 piconewtons or larger by Fe3O4/CaO2 aggregations) and induce the generation of intracellular reactive oxygen species (ROS), and the VMF-triggered Fe3O4/CaO2 is shown to generate additional intracellular ROS. Upon exposure to a VMF, the cell killing efficiency and tumor growth inhibition were further significantly improved by Fe3O4/CaO2 through CDT, magnetomechanical force, force-induced ROS, and the cytotoxicity of Ca2+ ions. In addition, the Fe3O4/CaO2 nanoenzymes and VMF-induced treatment are shown to be safe for mice. The results of this study open the door for treating solid tumors without inducing multidrug resistance through the combination of CDT and force. [ABSTRACT FROM AUTHOR]

Keeping steps ahead of the bacteria in the race for more efficacious antibacterial strategies is increasingly difficult with the advent of bacterial resistance genes. Herein, we engineered copper sulfide nanoclusters (CuS x NCs) with variable sulfur defects for enhanced dual-treatment of bacterial infections by manipulating photothermal effects and Fenton-like activity. Next, by encasing CuS x NCs with a complex mixture of amino acids and short peptides derived from Luria-Bertani bacterial culture media as a protein corona, we managed to coax E. Coli to take up these CuS x NCs. As a whole, Amino-Pep-CuS x NCs was perceived as a food source and actively consumed by bacteria, enhancing their effective uptake by at least 1.5-fold greater than full length BSA protein BSA-corona CuS x NCs. Through strategically using defect-engineering, we successfully fine-tune photothermal effect and Fenton-like capacity of CuS x NCs. Increased sulfur defects lead to reduced but sufficient heat generation under solar-light irradiation and increased production of toxic hydroxyl radicals. By fine-tuning sulfur defects during synthesis, we achieve CuS x NCs with an optimal synergistic effect, significantly enhancing their bactericidal properties. These ultra-small and biodegradable CuS x NCs can rapidly break down after treatment for clearance. Thus, Amino-Pep-CuS x NCs demonstrate effective eradication of bacteria both in vitro and in vivo because of their relatively high uptake, optimal balanced photothermal and chemodynamic outcomes. Our study offers a straightforward and efficient method to enhance bacterial uptake of next generation of antibacterial agents., Competing Interests: David Tai Leong is an associate editor for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)