Bacterial biofilms cause persistent infectious diseases and create tremendous obstacles to anti-infection treatment. [5,6] Epidemiological evidence has shown that biofilm formation poses a risk of chronic infection for clinical treatments, particularly in implant patients [7,8] such as cardiovascular grafts, fracture treatment, and orthodontic treatment. [9,10] If the biofilm infection is not cured in time, the long-term use of antibiotics to treat chronic infection may further aggravate the negative impact of antibiotics on the human body.The particular structure and components of the biofilm hinder the penetration efficiency of drugs and reduce the therapeutic effect of antibiotics, causing the hazard of bacterial biofilms. [11] In addition, some drug-resistant bacteria that inhabit the biofilms could secrete hydrolases (e.g., β-lactamases) to degrade antibiotics, making antibiotics ineffective. [12] In biofilms, the matrix, which accounts for most of the dry mass, possesses diverse functions such as the external digestive system, recycling center, gene pool, and nutrient source. [13,14] Biofilm organisms produce extracellular polymeric substances (EPS), primarily comprising exopolysaccharides, proteins, lipids, and extracellular DNA (eDNA), varying according to the environmental conditions. [15,16] EPS protects the organism from drying, oxidization, charged biocides, antibiotics, metal cations, and the host's immune defenses. [13,17,18] Additionally, EPS limits the diffusion of nutrients, creating a nutrient-deficient environment, further resulting in the slow metabolism of bacteria within the biofilm, making the bacteria less sensitive to antibiotics. [19] First, obstruction of the biofilm matrix results in extremely poor antibiotic and nutrient permeability. The aggregation of cations, such as Ca 2+ and Mg 2+ , in biofilms, promotes crosslinking between polymeric polysaccharide molecules, increasing both the viscosity and binding forces of the biofilm matrix. [20] The hydrophilic-hydrophobic properties of EPS also influence the drug penetration effect, which is related to the hydration state of EPS. [21,22] Furthermore, EPS helps immobilize bacterioplankton. The embedded bacteria in the biofilm show intense interconnections and produce stronger intercellular signal communication, a process called quorum sensing (QS). [23] Benefitting from QS, a relatively Bacterial biofilm-related infectious diseases severely influence human health. Under typical situations, pathogens can colonize inert or biological surfaces and form biofilms. Biofilms are functional aggregates that coat bacteria with extracellular polymeric substances (EPS). The main reason for the failure of biofilm infection treatment is the low permeability and enrichment of therapeutic agents within the biofilm, which results from the particular features of biofilm matrix barriers such as negatively charged biofilm components and highly viscous compact EPS structures. Hence, developing novel therapeutic strategies with enhanced biofilm penetrability is...

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