Mechanism and nanotechnological-based therapeutics for tolerance and resistance of bacterial biofilms.

Bacterial biofilms are one of the most relevant drivers of chronic and recurrent infections and a significant healthcare problem. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure and low drug permeability, leading to tolerance and resistance of biofilms to antibiotics and to host responses. Within a biofilm, microbial cells show increased tolerance to both immune system defense mechanisms and antimicrobials than the same cells in the planktonic state. It is one of the key reasons for the failure of traditional clinical drug to treat infectious diseases. Currently, no drugs are available to attack bacterial biofilms in the clinical setting. The development of novel preventive and therapeutic strategies is urgently needed to allow an effective management of biofilm-associated infections. Based on the properties of nanomaterials and biocompatibility, nanotechnology had the advantages of specific targeting, intelligent delivery and low toxicity, which could realize efficient intervention and precise treatment of biofilm-associated infections. In this paper, the mechanisms of bacterial biofilm resistance to antibiotics and host response tolerance were elaborated. Meanwhile, This paper highlighted multiple strategies of biofilms eradication based on nanotechnology. Nanotechnology can interfere with biofilm formation by destroying mature biofilm, modulating biofilm heterogeneity, inhibiting bacterial metabolism, playing antimicrobial properties, activating immunity and enhancing biofilm penetration, which is an important new anti-biofilm preparation. In addition, we presented the key challenges still faced by nanotechnology in combating bacterial biofilm infections. Utilization of nanotechnology safely and effectively should be further strengthened to confirm the safety aspects of their clinical application.