Gram-negative bacteria recognition and photodynamic elimination by Zn-DPA based sensitizers

Zuokai Wang1, Shuang Zeng2, Yifu Hao2

  • 1State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials, Dalian University of Technology, Dalian, 116024, PR China.

Biomaterials
|April 18, 2024
PubMed

Insights

New photosensitizers can distinguish and eliminate drug-resistant Gram-negative bacteria. NBS-DPA-Zn differentiates bacteria, while NBS-2DPA-Zn offers broad-spectrum antibacterial photodynamic therapy (APDT) and biofilm eradication.

Area of Science:

  • Biochemistry
  • Materials Science
  • Microbiology

Background:

  • Antibiotic resistance is a growing global health threat, necessitating novel antibacterial strategies.
  • Antibacterial photodynamic therapy (APDT) utilizes photosensitizers to generate reactive oxygen species for bacterial elimination.
  • Existing APDT photosensitizers often show limited efficacy against Gram-negative bacteria.

Purpose of the Study:

  • To design and synthesize novel photosensitizer conjugates for targeted Gram-negative bacteria elimination.
  • To investigate the differential bacterial recognition and antibacterial activity of NBS-DPA-Zn and NBS-2DPA-Zn conjugates.
  • To evaluate the potential of NBS-2DPA-Zn in a hydrogel formulation for treating mixed bacterial infections.

Main Methods:

  • Synthesis of NBS-DPA-Zn and NBS-2DPA-Zn conjugates by linking NBS photosensitizer with zinc-dipicolylamine (Zn-DPA).
  • Evaluation of bacterial recognition capabilities based on cationic character and Zn-DPA interactions.
  • Assessment of APDT efficacy against Gram-negative bacteria and biofilms, including in a diabetic mouse model with Pluronic hydrogel formulation.

Main Results:

  • NBS-DPA-Zn demonstrated specific recognition of *P. aeruginosa* among Gram-negative bacteria.
  • NBS-2DPA-Zn exhibited broad-spectrum antibacterial activity against Gram-negative bacteria and eradicated biofilms.
  • NBS-2DPA-Zn formulated in Pluronic hydrogel showed promising results in a mixed bacterial diabetic mouse model.

Conclusions:

  • The designed NBS-DPA-Zn and NBS-2DPA-Zn conjugates offer a novel approach for functional bacterial identification and elimination.
  • Intelligent regulation of Zn-DPA moieties allows for tailored antibacterial strategies against specific or multiple bacterial pathogens.
  • These findings highlight the potential of advanced photosensitizer conjugates for combating drug-resistant bacterial infections and biofilms.