Peroxidase-like copper-doped carbon-dots embedded in hydrogels for stimuli-responsive bacterial biofilm elimination and wound healing.

Abstract

Bacterial biofilms and their microenvironment are significant challenges that must be faced in the design of antibacterial drugs. Microenvironment-responsive mimetic peroxidases (POD) have been demonstrated to be an efficient solution to eliminating bacterial biofilms. However, they inevitably require additional H₂O₂ and/or acid due to the poor permeabilities towards biofilms. Herein, we report POD-like copper-doped carbon dots (named CuCD1) synthesized through a facile microwave-assisted carbonization manner. The characteristics of ultrasmall size (< 5 nm) and positive charge enabled it to possess good penetrability toward bacterial biofilm. As expected, CuCD1 showed great damage to bacteria due to the generation of hydroxyl radicals (•OH), which originated from the catalytic decomposition of endogenous H₂O₂ under a weak acid bacterial biofilm microenvironment. This highly increased oxidative stress resulted in the alteration of cell membrane permeability, subsequent cell death, and the final eradication of bacterial biofilm and the exposed bacteria. Moreover, to verify the practicality in vivo, CuCD1 was introduced to a routine hydrogel that was crosslinked by carboxymethyl chitosan (CMCS) and oxidized dextran (ODEX). In comparison with the control groups, the composite hydrogel, i.e., CuCD1-CMCS-ODEX revealed better antibacterial performance and thus accelerated wound healing and collagen disposition. This work would open opportunities to design CDs-based biofilm microenvironment-responsive antibacterial nanoagents. STATEMENT OF SIGNIFICANCE: (1) Ultrasmall size, positively charged, peroxidase (POD)-like CuCD1 were designed and harvested by a facile microwave-assisted carbonization method. (2) CuCD1 revealed a competitive in vitro antibacterial performance, good penetrability, and microenvironment-responsive clearing capacity towards bacterial biofilm. (3) By composing with CMCS-ODEX hydrogel, the composite hydrogel could continuously eliminate bacteria, promote wound healing, as well as collagen disposition. (4) This work would provide a new strategy in the design of CDs-based biofilm microenvironment-responsive antibacterial nano-agents.