<p>The growing threat of multidrug-resistant (MDR) bacterial infections requires novel antimicrobial approaches that bypass traditional resistance mechanisms. Herein, a core–shell Si@C/CoO structure is engineered, featuring a shell of carbon networks that confine quantum cobalt oxides and are supported on silica nanospheres. This novel platform synergistically integrates photothermal therapy and photodynamic therapy antibacterial mechanisms. Leveraging the synergistic interaction between the carbon layer and ultrafine CoO, Si@C/CoO achieves a remarkably high photothermal conversion efficiency (<i>η</i> = 42.65%), which is twice as high as that of gold nanorods (21%). Simultaneously, ultrafine CoO within the carbon framework induces sustained reactive oxygen species (ROS) generation, enabling dual-modal bacterial eradication and overcoming critical limitations of PDT. The platform demonstrates broad-spectrum efficacy against MDR pathogens, eliminating 100% of both MDR <i>S. aureus</i> and MDR <i>E. coli</i> under brief (10&#xa0;min) near-infrared (NIR) irradiation, while exhibiting superior biocompatibility. Crucially, Si@C/CoO retains outstanding antimicrobial performance in complex biological wastewater, achieving near-complete (≈100%) bacterial inhibition even after 40 cycles of recovery and reuse. Transcriptomic profiling reveals that Si@C/CoO nanospheres exert multi-target antibacterial effects under NIR exposure. Key ribosomal genes (e.g., rpsT, rpsU) are downregulated, disrupting protein synthesis, while suppressed tricarboxylic acid cycle (sdhC, fumA) and oxidative phosphorylation genes compromise energy metabolism. Concurrently, upregulated oxidative stress genes (mhpF, mhpE) reflect bacterial countermeasures against ROS, yet metabolic repair genes (phnP, phnI) are inhibited. This multifaceted targeting spans protein synthesis, energy metabolism, and oxidative stress and thereby reduces the risk of resistance development compared with single-target antibiotics, showcasing great potential in biological wastewater disinfection and combating antimicrobial resistance.</p> Graphical Abstract <p></p>

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Synergistic multi-target antimicrobial nanotherapy: near-infrared-triggered carbon-shell confined quantum CoO for efficient photothermal eradicating resistant pathogens

  • Jun Wang,
  • Shui-Xia Wan,
  • Rong-Rong Du,
  • Shu-Xian Hou,
  • Yao Xiao,
  • Guo-Qiang Yang,
  • Xin-Xin Liu,
  • Jun Ge,
  • Zhi-Ru Tao,
  • Clarissa Passawe,
  • Rong-Rong Li,
  • Fu Yang

摘要

The growing threat of multidrug-resistant (MDR) bacterial infections requires novel antimicrobial approaches that bypass traditional resistance mechanisms. Herein, a core–shell Si@C/CoO structure is engineered, featuring a shell of carbon networks that confine quantum cobalt oxides and are supported on silica nanospheres. This novel platform synergistically integrates photothermal therapy and photodynamic therapy antibacterial mechanisms. Leveraging the synergistic interaction between the carbon layer and ultrafine CoO, Si@C/CoO achieves a remarkably high photothermal conversion efficiency (η = 42.65%), which is twice as high as that of gold nanorods (21%). Simultaneously, ultrafine CoO within the carbon framework induces sustained reactive oxygen species (ROS) generation, enabling dual-modal bacterial eradication and overcoming critical limitations of PDT. The platform demonstrates broad-spectrum efficacy against MDR pathogens, eliminating 100% of both MDR S. aureus and MDR E. coli under brief (10 min) near-infrared (NIR) irradiation, while exhibiting superior biocompatibility. Crucially, Si@C/CoO retains outstanding antimicrobial performance in complex biological wastewater, achieving near-complete (≈100%) bacterial inhibition even after 40 cycles of recovery and reuse. Transcriptomic profiling reveals that Si@C/CoO nanospheres exert multi-target antibacterial effects under NIR exposure. Key ribosomal genes (e.g., rpsT, rpsU) are downregulated, disrupting protein synthesis, while suppressed tricarboxylic acid cycle (sdhC, fumA) and oxidative phosphorylation genes compromise energy metabolism. Concurrently, upregulated oxidative stress genes (mhpF, mhpE) reflect bacterial countermeasures against ROS, yet metabolic repair genes (phnP, phnI) are inhibited. This multifaceted targeting spans protein synthesis, energy metabolism, and oxidative stress and thereby reduces the risk of resistance development compared with single-target antibiotics, showcasing great potential in biological wastewater disinfection and combating antimicrobial resistance.

Graphical Abstract