pH‐Triggered Size‐Tunable Silver Nanoparticles: Targeted Aggregation for Effective Bacterial Infection Therapy

Abstract

The rapid spread of drug‐resistant pathogens threatens human health. To address the current antibacterial dilemma, the development of antibiotic‐free strategies using nanotechnology is imperative. In this study, silver nanoparticles (Ag‐P&C NPs) with pH‐sensitive charge reversal and self‐aggregation capacities are successfully synthesized. In the acidic microenvironment of bacterial biofilms, protonation of the surface peptide enhances the affinity of Ag‐P&C NPs for bacteria, which can make Ag‐P&C NPs prone to target and penetrate into biofilms, and the self‐aggregated capacity helps Ag‐P&C NPs remain in biofilms for a long time to disrupt bacterial biofilm formation. In addition, biocompatible Ag‐P&C NPs are utilized in three types of bacteria‐infected animal models. They exhibit an excellent performance in killing bacteria, inhibiting plaque biofilms, and ameliorating inflammatory responses. In conclusion, this study offers new insights into antibiotic‐free antibacterial strategies, and exhibits promising application prospects.

Nanobiotics against antimicrobial resistance: harnessing the power of nanoscale materials and technologies

“…Silver NPs (AgNPs) attach to cell membrane, interact with membrane proteins, increase membrane porosity, enter and enhance generation of reactive oxygen species (ROS) hampering respiration, including bacterial cell lysis, and evoking inflammatory reactions [69]. A recent study shows that the pH-triggered aggregation of AgNPs favors their penetration into bacterial biofilms [70]. The large aggregated AgNPs remain in the biofilms for a long time, disrupt bacterial biofilm formation, and exhibit better antibacterial activity than traditional AgNPs [70].…”

“…A recent study shows that the pH-triggered aggregation of AgNPs favors their penetration into bacterial biofilms [70]. The large aggregated AgNPs remain in the biofilms for a long time, disrupt bacterial biofilm formation, and exhibit better antibacterial activity than traditional AgNPs [70]. Gold NPs (AuNPs) exert bactericidal effects by accumulating on the cell surface credited to heavy electrostatic forces accompanied by cytoplasmic leakage and cell death [71].…”

“…Typically, graphene-based NPs, regarded as "nanoknives" or MoS 2 , MnO 2 with sharp edges are known to physically disintegrate bacteria cell wall [97]. AgNPs cause jamming of oxidative phosphorylation due to dissipation of proton motive force as a result of anchoring into the bacterial membrane [70,98]. Fullerenes kill bacteria by physically rupturing their cell wall integrity [99].…”

“…The large aggregated AgNPs have been shown to exhibit better penetration ability in infected areas and longer retention in the bacterial biofilms, disrupting biofilm formation and effectively eliminating bacterial populations [70]. Aggregated AgNPs would also exhibit longer retention periods in tissues and the exocytosis from the cells would be relatively slower than small non-aggregated particles, adding to their therapeutic implications [70].…”

Metal-based nano-delivery platform for treating bone disease and regeneration

“…Metal elements exhibit excellent antibacterial and anti-oxidative stress effects ( Makvandi et al, 2020 ), thereby facilitating synergistic anti-bone infection and osteoarthritis effects to the delivered components ( Luo et al, 2021 ); however, a few other metal elements can also endow nano-delivery systems with special targeted delivery ( Niculescu and Grumezescu, 2022 ), photodynamic therapy (PDT) ( He et al, 2022 ), thermodynamic therapy ( Boroushaki et al, 2022 ), bioimaging ( Zhong et al, 2021 ), and stimuli-responsive ( Hu et al, 2022 ) functions, which are more conducive to the efficient diagnosis and treatment of bone diseases or promote bone regeneration, and decrease the simple systemic side effects of drug use. A few of researchers reported that metal nanoparticles (NPs) can be used as nano-antibiotics because of their favorable antibacterial activities and significant potential to combat antibiotic resistance ( Cheng et al, 2022 ). In addition, studies have demonstrated that metal-based nanomaterials possess excellent mechanical properties as well as the intrinsic ability to significantly promote osseointegration, osteoconductivity, and osteoinduction, which has become crucial factors for bone regeneration ( Sobolev et al, 2019 ; Eivazzadeh-Keihan et al, 2020a ).…”