Antimicrobial Properties Of Two Nitrogen-doped Graphene Quantum Dots

Antimicrobial resistance is one of the biggest threats to global health,food security,and development today.The rapid emergence of resistant microorganisms is occurring worldwide.Misuse and overuse of antibiotics in humans and animals is accelerating the process,as well as poor infection prevention and control.Therefore,there is an urgent need to develop new antimicrobial drugs.Graphene quantum dots(GQDs),as a new type of zero-dimensional carbon nanomaterials,were widely applied in biomedicine field due to unique properties.In this study,two different nitrogen-doped GQDs were prepared based on different antimicrobial strategies,and their antimicrobial effects were studied.(1)Antibacterial research of P-GQD based on photothermal effect.For the first time,a water-soluble graphene quantum dot P-GQD was prepared by microwave synthesis using nitrocoronene and polyethyleneimine as precursors.P-GQD was graphitic nitrogen doped and carried positive charges.By adjusting the ratio of Ndoping of graphite,the performance of near-infrared response was endowed,and the light absorption range was extended to the near-infrared II region.The photothermal conversion efficiencies in the near-infrared region I(808 nm)and near-infrared region II(1064 nm)were 77.8% and 50.35%,respectively.In vitro antibacterial tests showed that P-GQD exhibited good photothermal antibacterial properties against Grampositive bacteria S.aureus and Methicillin-resistant S.aureus(MRSA),Gram-negative bacteria E.coli in the near infrared region I and II.And it was able to inhibit biofilm formation.P-GQD showed lower cytotoxicity and low hemolysis rate in vitro.The results of mouse experiments showed that P-GQD can effectively alleviate skin infection caused by MRSA and promote wound healing in the near-infrared Ⅱ region.(2)Antimicrobial research of J-GQD based on DNA major groove targeting.JGQD was prepared by acid-catalyzed solvothermal synthesis method using the small molecule drug Julolidine as a precursor.It has a unique amphiphilic structure with a large number of positive charges,surrounded by alkaline nitrogen heterocyclic clusters.In vitro experiments showed that J-GQD had good antimicrobial activity on E.coli,S.aureus,MRSA,L.monocytogenes,the endospores of B.subtilis and C.albicans.JGQD suppressed the formation of biofilm and killed the living cells in it.After J-GQD entered cells,it not only inhibited the activity of topoisomerase I,but also caused DNA fragmentation,cell rupture,and lead to cell death.J-GQD could reduce the hemolysis rate and enterotoxin content of MRSA.Transcriptomic data demonstrated that genes related to riboflavin biosynthesis,DNA repair,and transporters proteins were upregulated in MRSA under the stress of J-GQD.J-GQD combined with oxacillin sodium had a synergistic effect on MRSA.The results of mouse experiment showed that J-GQD was biosafe.It could accelerate skin wound healing and attenuate scarring caused by MRSA and C.albicans in mice.In conclusion,these two different nitrogen-doped GQDs have broad-spectrum antimicrobial activity based on different antimicrobial strategies.