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Studying Copper Nanoparticle-Induced Programmed Cell Death in Bacteria
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Self-Cascading Copper-Based Nanoassemblies Trigger Bacterial Cuproptosis-Like Death and Promote Wound Healing for

Tianji Feng1,2, Wenjie Fan1, Yin Zhang1

  • 1Eye Center, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou 310009, P. R. China.

ACS Nano
|April 29, 2026
PubMed

Insights

New nanoassemblies combat drug-resistant bacteria in diabetes. These engineered particles deliver antibacterial and anti-inflammatory effects, promoting tissue repair for diabetic complications.

Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Infectious Diseases

Background:

  • Diabetes mellitus causes immunosuppression, increasing infection susceptibility and complication severity.
  • Multidrug-resistant (MDR) pathogens, like methicillin-resistant Staphylococcus aureus (MRSA), complicate diabetes treatment.
  • Diabetic infections require innovative therapeutic strategies addressing both pathogen resistance and host immune dysfunction.

Purpose of the Study:

  • To engineer multifunctional nanoassemblies (DC/Cu) for treating MDR bacteria-induced diabetic infections.
  • To integrate antibacterial, anti-inflammatory, and tissue-reparative properties into a single therapeutic agent.
  • To investigate the mechanism of action of DC/Cu nanoassemblies against MRSA and their efficacy in diabetic models.

Main Methods:

  • Copper-coordinated self-assembly of carbon dots (CDs) and diclofenac sodium (DS) to form POD-like nanoassemblies (DC/Cu).
  • Assessment of DC/Cu's antibacterial activity, drug release kinetics, and mechanism of MRSA cell death (cuproptosis).
  • Evaluation of DC/Cu efficacy in MRSA-infected diabetic foot ulcer and keratitis animal models, assessing bacterial eradication, inflammation, and tissue regeneration.

Main Results:

  • DC/Cu nanoassemblies exhibit peroxidase-like activity, catalyzing H2O2 to induce lipid peroxidation and copper influx into MRSA.
  • Intracellular copper overload triggers a cuproptosis-like death pathway in MRSA by inhibiting Fe-S cluster proteins and disrupting the tricarboxylic acid cycle.
  • DC/Cu effectively eradicated MRSA, reduced inflammation, and promoted tissue regeneration in diabetic infection models.

Conclusions:

  • Multifunctional DC/Cu nanoassemblies offer a promising precision therapeutic approach for MDR pathogen-aggravated diabetic complications.
  • The engineered nanoassemblies demonstrate synergistic antibacterial, anti-inflammatory, and regenerative effects.
  • DC/Cu represents a novel strategy for combating challenging infections in diabetic patients.
Keywords:
cuproptosis-like deathdiabetic complicationsdrug-resistant bacteria infectionperoxidase-like activityself-cascading nanoassemblies

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