Design of pH-Responsive Dissociable Nanosystem Based on Carbon Dots with Enhanced Anti-biofilm Property and Excellent Biocompatibility.

Abstract

Bacterial biofilm poses a serious threat to human health, leading to increased and prolonged bacterial infections. How to solve the problem of eliminating biofilms effectively and rapidly while being nontoxic to normal cells is still a challenge. Here, we design a pH-sensitive anti-biofilm nanosystem formed by self-assembly between negatively charged carboxyl groups of poly(ethylene glycol_-COOH-polyethylenimine-2,3-dimethylmaleic anhydride (PPD) and positively charged amines on the surface of carbon dots derived from the ashes of calcined l-lysine powder (CDLys) (PPD@CDLys for short). The outmost copolymer could make PPD@CDLys facilely diffuse into the dense biofilm and reverse to be positively charged via hydrolysis, which lead to the acid-triggered disassembly of the nanosystem. After hydrolyzation, PPD would turn into a biocidal cationic polymer, which is prone to attaching on bacteria inside the biofilm and efficiently killing them. In addition, the released CDLys could induce intracellular reactive oxygen species (ROS) across the whole biofilm to degrade the matrix of extracellular polymer substances and kill resident bacteria deep into the biofilm. Finally, the prepared nanosystem effectively inhibits the formation of Staphylococcus aureus biofilm and rapidly destroys the mature biofilm by the synergy antibacterial effects of the cation and ROS. We also evaluate the biocompatibility of the nanocomposites. The results show that PPD@CQDLys has no toxicity to L929 and 3T3 cells and exhibits a zero hemolytic rate even when the concentration is up to 2000 μg/mL. The outstanding biocompatibility coupled with rapid anti-biofilm ability of the nanosystem presents an opportunity for it to be utilized as an effective pH-responsive and targetable anti-biofilm agent for controlling bacterial infections.