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Published on: September 28, 2016
A Mucous Permeable Local Delivery Strategy Based on Manganese-Enhanced Bacterial Cuproptosis-like Death for Bacterial
Shiyuan Hua1,2,3, Huiqun Hu4, Jin Liu2
1Eye Center, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou310009, China.
Abstract:
Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.
Insights
This study introduces a novel copper nanoparticle that induces cuproptosis-like cell death in aerobic bacteria, offering a new treatment for bacterial pneumonia. The nanoparticle effectively targets lung infections while minimizing systemic toxicity.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Nanotechnology
Background:
- Bacterial pneumonia presents significant global health challenges due to high morbidity and mortality.
- Antibiotic resistance and bacterial biofilms necessitate innovative therapeutic strategies.
- Existing metal-based antibacterial materials face limitations in oxygen-rich lung environments.
Purpose of the Study:
- To design a copper composite nanoparticle capable of inducing cuproptosis-like death in aerobic bacteria.
- To overcome in vivo application challenges for cuproptosis-based therapies.
- To develop an effective treatment for aerobic bacterial pneumonia with reduced systemic toxicity.
Main Methods:
- Incorporation of manganese dioxide to deplete glutathione and enhance copper's antibacterial action.
- Development of positively hydrophilic modified composite nanoparticles for efficient lung mucus penetration.
- Local administration of nanoparticles to the infected site for targeted copper ion release.
- Utilizing the acidic environment of infection sites to accelerate copper ion release and biofilm disruption.
Main Results:
- The copper composite nanoparticle effectively induced cuproptosis-like death in aerobic lung bacteria.
- Manganese dioxide incorporation enhanced antibacterial efficacy by depleting glutathione.
- The nanoparticle system demonstrated efficient penetration of lung mucus and targeted drug delivery.
- Rapid release of copper ions in acidic infected environments synergistically disrupted bacterial biofilms.
Conclusions:
- The developed copper composite nanoparticle offers a promising therapeutic strategy for aerobic bacterial pneumonia.
- The nanoparticle system effectively treats pneumonia by inducing bacterial cell death and disrupting biofilms.
- Local administration and targeted ion release minimize systemic toxicity associated with copper-based therapies.
