4.8 Article

Intelligent bio-assembly imaging-guided platform or real-time bacteria sterilizing and infectious therapy

Journal

NANO RESEARCH
Volume 15, Issue 5, Pages 4164-4174

Publisher

TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-021-3998-3

Keywords

bacterial microenvironment response; self-assembled Fe@Au-DNA complexes; bacterial fluorescence bioimaging; bacteria inactivation; wound healing

Funding

  1. National Key Research and Development Program of China [2017YFA0205300]
  2. National Natural Science Foundation of China [82027806, 82061148012, 91753106]
  3. Primary Research & Development Plan of Jiangsu Province [BE2019716]
  4. ISF-NSFC Joint Research Program [3258/20]

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Bacterial infections are a growing health issue, and timely diagnosis and treatment are crucial. This paper presents a multifunctional nanotheranostics platform based on the unique micro-environment of bacterial infections, which allows for bacterial bioimaging and simultaneous inactivation. The experiments show that the self-assembled nanoclusters can emit fluorescence in bacterial infections and efficiently sterilize bacteria through multiple mechanisms. Furthermore, the nanotheranostics platform exhibits good performance in in vivo tests and accelerates wound healing in bacterial infections.
Bacterial infection is rising as a threatening health issue. Because of the present delay in early diagnosis of bacterial diseases as well as the abuse of antibiotics, it has become a vital issue in the development of in-time detection and therapy of bacterial infections. Herein, we designed a multifunctional nanotheranostics platform based on the unique micro-environment of bacterial infections to achieve specific bioimaging and simultaneous inactivation of the target bacteria. We showed that in bacterial infections, the metal precursors (i.e., HAuCl4, FeCl2, and herring sperm DNA) could be readily bio-self-assembled to multifunctional nanoclusters (NCs) that exhibit luminescence, in which AuCl4- was biosynthesized via reductive biomolecules such as NADPH to the fluorescent AuNCs. The DNA may assist as an encapsulation and delivery vector, and Fe2+ served as a fluorescence intensifier and reduced reactive oxygen species (ROS) to produce the iron oxides. While the bacteria were being visualized, the microenvironment-responsive NCs were enabled to sterilize bacteria efficiently due to electrostatic effect, cell membrane destruction, inhibition of biofilm formation, and ROS accumulation. Besides, the bio-responsive self-assembled NCs complexes contributed to accelerating bacteria-infected wound healing and showed negligible side effects in long-term toxicity tests in vivo. Also, intracellular molecules involved in microenvironmental response were investigated. The work may become an effective strategy for the detection and real-time sterilization of intractable bacterial infections.

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