Cationic Silver Nanoclusters as Potent Antimicrobials against Multidrug-Resistant Bacteria

Abstract

Bacterial multidrug resistance (MDR) is a serious healthcare issue caused by the long-term subtherapeutic clinical treatment of infectious diseases. Nanoscale engineering of metal nanoparticles has great potential to address this issue by tuning the nano–bio interface to target bacteria. Herein, we report the use of branched polyethylenimine-functionalized silver nanoclusters (bPEI–Ag NCs) to selectively kill MDR pathogenic bacteria by combining the antimicrobial activity of silver with the selective toxicity of bPEI toward bacteria. The minimum inhibitory concentration of bPEI–Ag NCs was determined against 12 uropathogenic MDR strains and found to be 10- to 15-fold lower than that of PEI and 2- to 3-fold lower than that of AgNO3 alone. Cell viability and hemolysis assays demonstrated the biocompatibility of bPEI–Ag NCs with human fibroblasts and red blood cells, with selective toxicity against MDR bacteria.

Nanosilver Mitigates Biofilm Formation via FapC Amyloidosis Inhibition

“…Below 250 × 10 −9 m , the antibiofilm activity of AgNPs became less prominent while the bacteria remained intact. At concentrations higher than 1 × 10 −6 m , the bactericidal activity of AgNPs eliminated the availability of viable bacteria from establishing biofilm . The in vitro anti‐FapC activities of AgNPs/AgNCs were correlated with their antibiofilm activity.…”

“…Cationic bPEI was employed to graft two types of Ag nanostructures ( Figure A,B) by chemical reduction . The size, morphology, and zeta potential of the nanoparticles are summarized in Figure 1C–H.…”

“…For example, cationic AgNPs are more toxic to the net negatively charged bacterial cells, as they promote membrane permeability and reduce bacterial drug efflux . In comparison, ultrasmall AgNCs (<3 nm) can target MDR bacteria by a membrane disruption mechanism and act as a broad spectrum antimicrobial agent . Motivated by the tremendous health implications of the gut microbiota as well as the urgent need to develop safe and potent nanobactericides against a range of human diseases, here, we examined the interactions between P. aeruginosa biofilms and AgNPs/AgNCs from the unique perspective of FapC amyloidosis.…”

“…Our working hypothesis is that we can compromise bacterial viability by weakening the bacterial biofilm through a reduction of functional amyloid formation. AgNPs/AgNCs were synthesized via the chemical reduction method by adjusting the ligand to reductant ratio, and were functionalized with cationic branched polyethylenimine (bPEI) polymer. bPEI coating enhances the interaction of nanoparticles with amyloid proteins and negatively charged P. aeruginosa , and is known for its interaction with bacterial surface and its associated bactericidal activities …”

The Use of Nanomedicine for Targeted Therapy against Bacterial Infections

“…Recently, the MIC of silver nanoclusters functionalized with branched polyethylenimine (bPEI−Ag NCs) was defined against twelve pathogenic MDR bacteria [49]. The results revealed that a 10 to 15-fold lower MIC was found for nanoparticles than that of PEI and from two to three times lower than that of lonely silver nitrate and the noticed wide range antibacterial activity can be assigned to the positive character of hydrophobic surface ligands that simplify the action of bPEI−Ag NCs with bacterial cells that initiates membrane injury, besides liberation of silver ions from the nanocluster compound [49]. By using a new seed growth synthesis, the coating of bulk glass materials with silver nanoplates was achieved.…”