Owing to their excellent photoluminescence (PL) properties, good biocompatibility, and low toxicity, graphene quantum dots (GQDs) are widely applied in bioimaging, biosensing, and so forth. However, further development of GQDs is limited by their synthetic methodology and unclear PL mechanism. Therefore, it is urgent to find efficient and universal methods for the synthesis of GQDs with high stability, controllable surface properties, and tunable PL emission wavelength. By coating with polyethyleneimine (PEI) of different molecular weights, blue-, yellow-, and red-emitting GQDs were successfully prepared. By transmission electron microscopy, atomic force microscopy, and dynamic light scattering, the characterization of size and morphology revealed that blue-emitting PEI1800 GQDs were monocoated, like jelly beans, and red-emitting PEI600 GQDs were multicoated, like capsules. The amidation reaction between carboxyl and amide functional groups played an important role in the coating process, as evidenced by IR spectroscopy and theoretical calculation with density functional theory B3LYP/6-31G*. The PL-tunable GQDs exhibited an excellent chemical stability and extremely low cytotoxicity, and they had been shown to be feasible for bioimaging, making these GQDs highly attractive for a wide variety of applications, including multicolor imaging and bioanalysis.Keywords: cellular imaging; coating nanomaterials; Graphene quantum dots; photoluminescence mechanism; photoluminescence tunable; polyethyleneimine;

Pb2+ exposure in humans occurs mainly through air inhalation, food and water uptake which has been shown to be generally associated with numerous body functions such as the central and peripheral nervous systems, the red blood cells, the kidneys and the liver. It has been reported that the liver is the storage site and an important primary target in Pb2+ toxicity, and the hepatotoxicity of Pb2+ could be resulted from the impairment of the liver mitochondria. In this study, several mitochondrial dysfunctions following the addition of Pb2+ (10–160 μM) were investigated. We found that Pb2+ inhibited the enzyme activities of mitochondrial respiratory complexes and complex III was the major source of Pb2+-induced significant reactive oxygen species (ROS) formation. As a consequence, our results showed that Pb2+ induced significant progress in mitochondrial lipid peroxidation, adenosine triphosphate (ATP) consumption and glutathione (GSH) oxidation. On the other hand, Pb2+ induced marked changes in mitochondrial permeability transition (MPT) accompanied by mitochondrial swelling, mitochondrial membrane potential collapse, mitochondrial membrane fluidity decrease and cytochrome c (Cyt c) release. Additionally, several mitochondrial MPT inhibitors and chelators were utilized to determine the possible interaction sites of Pb2+ on mitochondria. In general, our data supported that the Pb2+-induced liver toxicity was a result of the disruptive effect on the mitochondrial respiratory complexes. This disruptive effect caused oxidative stress and MPT, which led to mitochondrial dysfunctions and even cell death signalling via mitochondrial permeability transition pore (MPTP) opening and Cyt c release.

•MPA-CdTe QDs had a stronger effect on MPT than TGA-CdTe QDs.•The weaker effect of TGA-CdTe QDs on MPT might be owing to their better stability and thus less amount of released Cd2+.•Surface ligands play an important role in the toxicity of CdTe quantum dots at the sub-cellular level.The potential toxicity of Quantum dots (QDs) should be assessed comprehensively for their fast spreading applications. Many studies have shown the toxicity of QDs is associated with their surface ligands. In this work, two analog ligands with one carbon difference, 2-mercaptoacetic acid (TGA) and 3-mercaptopropionic acid (MPA) were used as coating materials in the syntheses of two types of CdTe QDs with similar physicochemical properties. Then the biological effects of QDs on isolated mitochondria were studied. It was found that the two types of QDs could impair mitochondrial respiration and induce mitochondrial permeability transition (MPT). However, as compared with TGA-CdTe QDs, MPA-CdTe QDs had a stronger effect on MPT. The weaker effect of TGA-CdTe QDs on MPT might be owing to their better stability and thus less amount of released Cd2+, which could be further explained by the stronger affinity between the ligand (TGA) and the cadmium complexes in the crystal growth of QDs. These results highlighted the importance of ligands responsible for the toxicity of QDs at the sub-cellular level.Download high-res image (228KB)Download full-size image

Although cation exchange (CE) has been studied for many years and some mechanisms were proposed, there is still a knowledge gap in CE and problems such as the need for high temperature and it being time-consuming are still unaddressed. We developed a new mild strategy for CE by introducing a new ideal template and first applied this doping strategy to detect Cd2+ and Hg2+. This strategy adopted Mn-doped ZnSe quantum dots (QDs) as the template and the introduction occurs via a two-step CE reaction: first Zn2+ was partially substituted by X (X = Cd2+, Hg2+, Cu2+, Ag+ or Pb2+), later Mn2+ (in the deep structure of QDs) was substituted by X. Remarkably, Mn2+ in the lattice can be easily substituted by a dopant and its replacement by a dopant helps to bury the metal ions. The ultra-fast introduction of Cd2+ and Hg2+ (70 minutes for Cd2+ and 19 minutes for Hg2+) was realized at room temperature; other metal ions such as Ag+, Cu2+ and Pb2+ can be buried at 50 °C. This mild reaction temperature offers a solution for introducing impurities without sacrificing the interfacial structure of nanocrystals. HRTEM, XPS and ICP measurements were applied to analyze the introduction process. Furthermore, the spectroscopic method was employed to analyze the introduction, migration and distribution of metal ions. Then, we proposed a mechanism for the chemical conversion of nanocrystals by CE. Through this strategy, full-color light-emitting doped QDs were fabricated. Strikingly, a new turn-on probe for the detection of Cd2+ and Hg2+ with improved selectivity was developed by adopting this doping strategy. The detection limit is 36 nM for Cd2+ and 20 nM for Hg2+, which is competitive with the limit of detection reported by other groups using QDs as sensors.

Silver materials have been widely used as antimicrobial agents. Notably, silver nanoparticles have emerged as a new generation of nanoproducts for biomedical and environmental applications in recent years. However, ultrasmall silver nanoclusters (NCs) (∼2 nm) have rarely been used to kill bacteria and their antibacterial mechanisms have not yet been fully elucidated. Herein, we studied the antibacterial activities of bifunctional fluorescent DHLA-AgNCs against three types of bacteria. The results showed that DHLA-AgNCs exhibited excellent antibacterial activities against Gram-negative E. coli, which could efficiently inhibit the growth of E. coli DH 5α and E. coli DSM 4230 cells at a concentration of 15 and 10 μg mL−1, respectively. Meanwhile AgNCs demonstrated no apparent antibacterial activity against Gram-positive S. aureus. Then, the antibacterial mechanisms of AgNCs were systematically investigated. We found that AgNCs affected the growth of different E. coli strains in different ways. AgNCs inhibited the growth of E. coli DH 5α mainly through damaging the outer cellular membrane and permeating into the cells, followed by the antibacterial effect of the internalized AgNCs and released silver ions. AgNCs, however, inhibited the growth of E. coli DSM 4230 cells mainly through diffusing into E. coli DSM 4230 cells and damaging their respiratory chain. These results clearly indicated that different bacterial strains (e.g. different E. coli strains) should be taken into consideration in future studies. Our work facilitates further investigation of the design of new antibacterial silver nanomaterials with different sizes.

The amino naphthalene 2-cyanoacrylate (ANCA) probe is a kind of fluorescent amyloid binding probe that can report different fluorescence emissions when bound to various amyloid deposits in tissue, while their interactions with amyloid fibrils remain unclear due to the insoluble nature of amyloid fibrils. Here, all-atom molecular dynamics simulations were used to investigate the interaction between ANCA probes with three different amyloid fibrils. Two common binding modes of ANCA probes on Aβ40 amyloid fibrils were identified by cluster analysis of multiple simulations. The van der Waals and electrostatic interactions were found to be major driving forces for the binding. Atomic contacts analysis and binding free energy decomposition results suggested that the hydrophobic part of ANCA mainly interacts with aromatic side chains on the fibril surface and the hydrophilic part mainly interacts with positive charged residues in the β-sheet region. By comparing the binding modes with different fibrils, we can find that ANCA adopts different conformations while interacting with residues of different hydrophobicity, aromaticity, and electrochemical properties in the β-sheet region, which accounts for its selective mechanism toward different amyloid fibrils.

•Pentafluorophenyl substituent on the meso position of BODIPY leads to bright emission in the red region.•The fluorescent probes are sensitive enough to detect and image the endogenous thiols in living cells.•This is a rare example for the kinetics and thermodynamics of the reactions between the fluorescent probes and biothiols.Two highly selective red-emitting fluorescent “OFF-ON” probes (3a and 3b) with a BODIPY core were designed and synthesized, based on the recovery of fluorescence upon the cleavage of the fluorescence quenching unit of 2, 4-dinitrobenzenesulfonyl (DNBS) by biothiols. The probes showed 43-fold (3a, λem = 610 nm) and 33-fold (3b, λem = 582 nm) fluorescence enhancement respectively in the presence of biothiols. Compared with 3b, the introduction of five strong electron-withdrawing fluorine atoms in 3a, not only caused a red shift of the emission maximum for 28 nm, but also increased the fluorescence enhancement. Since they had stable fluorescence emission within physiological pH range, the two probes can be applied in imaging of living cells. In contrast, no such fluorescence response was observed in the cells pre-treated with N-ethylmaleimide (NEM), a well-known thiol scavenger. A non-linear curve-fitting of high quality was used to fit the spectroscopic data to determine the pseudo-first-order rate constants and the chemical equilibrium constants at different given temperatures (e.g. 310 K, 298 K and 288 K). Activation energy (Ea) and thermodynamic parameters, including Gibbs free energy change (ΔG), enthalpy change (ΔH) and entropy change (ΔS), could be calculated. To the best of our knowledge, this was the first report for the chemical kinetics and thermodynamics of the reaction between the fluorescent probes and thiols. This work would greatly inspire the future design of even better fluorescent probes.The fluorescent probes are sensitive enough to detect and image the endogenous thiols in living cells. This is a rare example for the kinetics and thermodynamics of the reactions between the fluorescent probes and thiols.Download high-res image (243KB)Download full-size image

Quantum dots (QDs) are increasingly applied in sensing, drug delivery, biomedical imaging, electronics industries, etc. Consequently, it is urgently required to examine their potential threat to humans and the environment. In the present work, the toxicity of CdTe QDs with nearly identical maximum emission wavelength but modified with two different ligands (MPA and BSA) to mitochondria was investigated using flow cytometry, spectroscopic, and microscopic methods. The results showed that QDs induced mitochondrial permeability transition (MPT), which resulted in mitochondrial swelling, collapse of the membrane potential, inner membrane permeability to H+ and K+, the increase of membrane fluidity, depression of respiration, alterations of ultrastructure, and the release of cytochrome c. Furthermore, the protective effects of CsA and EDTA confirmed QDs might be able to induce MPT via a Ca2+-dependent domain. However, the difference between the influence of CdTe QDs and that of Cd2+ on mitochondrial membrane fluidity indicated the release of Cd2+ was not the sole reason that QDs induced mitochondrial dysfunction, which might be related to the nanoscale effect of QDs. Compared with MPA-CdTe QDs, BSA-CdTe QDs had a greater effect on the mitochondrial swelling, membrane fluidity, and permeabilization to H+ and K+ by mitochondrial inner membrane, which was caused the fact that BSA was more lipophilic than MPA. This study provides an important basis for understanding the mechanism of the toxicity of CdTe QDs to mitochondria, and valuable information for safe use of QDs in the future.

A bromine-substituted hydrazone derivative, named N′-(4-bromobenzylidene)-2-hydroxybenzohydrazide (BBH), and its unsubstituted analogue, named N′-benzylidene-2-hydroxybenzohydrazide (BH), have been synthesized by a simple and effective one-pot synthesis method. Their interactions with human serum albumin (HSA) were comprehensively studied employing spectroscopy, electrochemistry, and molecular docking. Our attention was largely on the thermodynamic properties of their binding to HSA, in order to evaluate the impact of a bromine atom in BBH to its biological activity comparing to BH. BBH is a stronger ligand with a binding constant of 105 L·mol−1 and formed a more stable complex with HSA compared with BH. The binding processes of both BBH and BH are mainly an enthalpy driven process occurring in site I, mainly bound by hydrogen bonding and the van der Waals force.

In this study, an acylhydrazone derivative, named N′-(2-chlorobenzylidene)-2-hydroxybenzo-hydrazide (NCH) has been synthesized by a one-pot synthesis method. Spectroscopy together with molecular modeling and electrochemistry were employed to investigate the binding behavior of NCH to serum albumin (SA), including human serum albumin (HSA) and bovine serum albumin (BSA), under physiological conditions. Unclassical static quenching has been proven in the fluorescence quenching of SA induced by NCH, due to the large activation energy requirement in the binding process. NCH was absorbed by both HSA and BSA with a 104 M−1 affinity constant. The primary binding driving force was the typical hydrophobic interaction occurring in Sudlow's site I of SA, while hydrogen bonds stabilized the NCH–SA complex and fixed the NCH configuration in the binding pocket. NCH could slightly destroy the polypeptide backbone and change the α-helix into an unordered ribbon. It was shown that NCH could efficiently bind with SA.

The toxicity of CdTe QDs modified with three different ligands, namely mercaptopropionic acid (MPA), N-acetyl-l-cysteine (NAC), and glutathione (GSH), were investigated via microcalorimetric, spectroscopic, and microscopic methods. The three ligand-modified QDs have nearly identical hydrodynamic size. The results of the calorimetric experiments and optical density measurements indicate that the QDs inhibited the growth of Gram-negative Escherichia coli. The toxicity order of the three QDs is MPA-CdTe QDs > GSH-CdTe QDs > NAC-CdTe QDs. The inhibitory effects of the QDs, cadmium chloride (CdCl2), MPA, and the CdCl2 and MPA mixture on E. coli growth indicate that the toxicity mechanism of QDs may be related to their bacterial adhesion. When dispersed in the cell suspensions, QDs tend to have their high surface energy reduced through adsorption to the bacterial surface, as confirmed by transmission electron microscopy and inductively coupled plasma atomic emission spectroscopy results. Furthermore, the effect of QDs on the membrane fluidity and permeability was investigated. GSH-CdTe QDs have a greater effect on the membrane function of E. coli than those of MPA-CdTe and NAC-CdTe QDs. This result may be attributed to the stronger lipophilicity of GSH compared with those of MPA and NAC.Graphical abstractHighlights► The toxicity order of QDs is MPA > GSH > NAC. ► The toxicity may be related to the adsorption of QDs to the surface of Escherichia coli. ► The adsorption induces a decrease in membrane fluidity and an increase in permeability. ► GSH-CdTe QDs have a greater effect on the cell membrane than others.

Zinc oxide nanoparticles (ZnO NPs) are increasingly applied in a diverse array of industrial and commercial products. Therefore, it is urgently required to characterize their toxic behavior. ZnO NPs have been reported to induce toxic effects at the levels of the individual organism, tissue, cell and DNA. However, little is known about the potential impacts of ZnO NPs at a subcellular level. In the present work, we investigated the toxicity of ZnO NPs to the isolated rat liver mitochondria. We found that treatment of mitochondria with ZnO NPs resulted in collapse of mitochondrial membrane potential (Δψ), swelling, depression of respiration, inner membrane permeabilization to H+ and K+, alterations of ultrastructure, release of cytochrome c, generation of reactive oxygen species (ROS), and Zn2+ liberation from ZnO NPs. These results suggested that ZnO NPs can increase the inner membrane permeability and impair the respiratory chain, thus leading to energy dissipation, oxidative stress and even apoptosis. This putative mechanism helps us learn more about the toxicology of this nanomaterial.

A novel hydrazone, 2-hydroxy-N′-(3-hydroxybenzylidene) benzohydrazide (HHB), has been designed, synthesized and characterized. HHB was designed to be an analogue of 311 and PIH with potential anticancer activity, and the IC50 towards HeLa cell was about 3.46 × 10−5 mol−1 L. The interactions of HHB with bovine serum albumin (BSA) had been investigated systematically by spectroscopy, electrochemistry, and molecular modeling under simulative physiological conditions. HHB bound BSA in the sub-domains IIA to form a ground-state complex, inducing the quenching of the intrinsic fluorescence emission, the change of absorption spectrum and the increase of electrical resistance of BSA. An adverse temperature dependence in the fluorescence quenching was detected and discussed to be a reasonable consequence of the big Ea requirement to overcome the obstructive amino acid residues in the entrance to the binding site, which were closely related to the natural structure of BSA and the molecular shape of HHB. The impact of metal ions, including Fe2+, Fe3+, Cu2+, Mg2+, Zn2+, Ca2+ and Al3+, towards the interactions of HHB and BSA has been investigated and they were found to affect the HHB–BSA interactions in a mild way.

This paper investigates the interactions between human serum albumin (HSA) and CdTe quantum dots (QDs) with nearly identical hydrodynamic size, but capped with four different ligands (MPA, NAC, and GSH are negatively charged; CA is positively charged) under physiological conditions. The investigation was carried out using fluorescence spectroscopy, circular dichroism (CD) spectra, UV–vis spectroscopy, and dynamic light scattering (DLS). The results of fluorescence quenching and UV–vis absorption spectra experiments indicated the formation of the complex of HSA and negatively charged QDs (MPA-CdTe, NAC-CdTe, and GSH-CdTe), which was also reconfirmed by the increasing of the hydrodynamic radius of QDs. The Ka values of the three negatively charged QDs are of the same order of magnitude, indicating that the interactions are related to the nanoparticle itself rather than the ligands. ΔH < 0 and ΔS > 0 implied that the electrostatic interactions play predominant roles in the adsorption process. Furthermore, it was also proven that QDs can induce the conformational changes of HSA from the CD spectra and the three-dimensional fluorescence spectra of HSA. However, our results demonstrate that the interaction mechanism between the positively charged QDs (CA-CdTe) and HSA is significantly different from negatively charged QDs. For CA-CdTe QDs, both the static and dynamic quenching occur within the investigated range of concentrations. According to the DLS results, some large-size agglomeration also emerged.Graphical abstractThe interaction between negatively charged QDs and HSA is a adsorption behavior, which depends on the nanoparticle itself rather than the coating molecule. However, the adsorption of HSA onto the surface of positively charged QDs would result in the aggregation of nanoparticles.Highlights► The interaction between negatively charged QDs and HSA is a adsorption behavior. ► A protein corona comes into being on the surface of negatively charged QDs. ► The adsorption of HSA to the positively charged QDs results in the aggregation of QDs. ► The aggregation of QDs can act as the nuclei adsorbing larger amounts of proteins.

The binding of vitamin C, L-ascorbic acid (AsA), with human serum albumin (HSA) was investigated by various spectroscopic techniques under simulated physiological conditions. The fluorescence quenching constants (KSV) at four different temperatures (292, 298, 304, and 310 K) were obtained. The thermodynamic parameters ΔH∘ and ΔS∘ were calculated to be 6.02 kJ⋅mol−1 and 84.55 J⋅mol−1⋅K−1 using the van’t Hoff equation. Additional experiments to determine the stoichiometry (n) were carried out using isothermal titration calorimetry (ITC) and cyclic voltammetry (CV). The distance, r, between AsA and the tryptophan residues of HSA was calculated to be 3.7 nm according to Förster’s non-radiation energy transfer theory. The effect of AsA on the conformation of HSA was studied by means of three dimensional fluorescence spectra and CD spectra. The results indicate that the presence of AsA resulted in a slight change of the HSA secondary structure. The effect of common ions on the binding of AsA to HSA was also examined.

An innovative trihexylsilylacetylene-containing BODIPY dye was designed and proved to be a highly selective, sensitive, and fast chromogenic and fluorescent chemodosimeter for fluorides.

The interaction between a cationic porphyrin and bovine serum albumin (BSA) was studied by using surface plasmon resonance (SPR) spectroscopy, which was combined with fluorescence quenching method and cyclic voltammetric method to confirm the binding kinetic results. In this paper, the SPR method used to study the drug-protein interaction was described in detail. The association rate constant, dissociation rate constant and the equilibrium association constant of porphyrin binding to BSA obtained from this method were 1067 ± 18.23 M−1 s−1, 0.01644 ± 0.00012 s−1, and 6.49 × 104 M−1, respectively. The equilibrium association constants obtained from the fluorescence quenching method and the cyclic voltammetric method were 1.102 × 105 M−1 and 1.21 × 105 M−1, respectively.

The interaction between 3-thiol-4-(2,4-dichlorobenzylideneamino)-5-methyl-4H-1,2,4-triazole (CBTZ) and bovine serum albumin (BSA) under physiological conditions was investigated by fluorescence, UV-vis absorption and circular dichroism (CD) spectroscopy as well as molecular modeling methods. The result of fluorescence experiment indicates the static quenching as a result of the formation of the CBTZ-BSA complex. The binding constants (Ka) at different temperatures were calculated according to the modified Stern-Volmer equation. The enthalpy change (ΔH) and entropy change (ΔS) were determined based on the van’t Hoff equation. Both negative ΔH and ΔS indicated that van der Waals and hydrogen-bonding forces were the dominant intermolecular forces to stabilize the CBTZ-BSA complex. Site marker competitive replacement experiments demonstrated that binding of CBTZ to BSA primarily took place in sub-domain IIA (Sudlow’s site I). The binding distance (r = 7.2 nm) between CBTZ and the tryptophan residue of BSA was estimated according to the theory of fluorescence resonance energy transfer (FRET). The conformational studies by circular dichroism (CD) and three-dimensional fluorescence spectroscopy showed that the presence of CBTZ induced minor changes of the secondary structure of BSA. Molecular modeling study further confirmed the binding mode obtained experimentally.

The interaction between coomassie brilliant blue G250 and human serum albumin was investigated by spectroscopic methods such as fluorescence quenching, synchronous fluorescence, 3D fluorescence spectra, circular dichroism spectra and UV–vis absorption as well as molecular modeling. The fluorescence quenching of human serum albumin by coomassie brilliant blue G250 was attributed to static interaction. The binding reaction was mainly enthalpy-driven. Both van der Waals and hydrogen bonding forces played major roles in stabilizing the coomassie brilliant blue G250–human serum albumin complex. The Stern–Volmer quenching constant (KSV) and corresponding thermodynamic parameters (ΔHΘ, ΔGΘ and ΔSΘ) were determined. Site marker competitive experiments indicated that coomassie brilliant blue G250 bound to site I (subdomain IIA) of human serum albumin. Molecular docking study further confirmed the binding mode obtained by experimental study. The conformational investigation demonstrated very minor micro-environmental and conformational changes in human serum albumin molecules.

Cationic porphyrins are potential antiprion drugs; however, the action mechanisms remain poorly understood. Herein, the interaction between a cationic porphyrin and recombinant human prion protein (rPrPC) was comprehensively studied by using surface plasmon resonance (SPR), fluorescence, resonance light scattering (RLS), and circular dichroism (CD) spectroscopy. The experimental results showed that the interaction between the cationic porphyrin and rPrPC was pH dependent. The equilibrium association constants obtained from SPR spectroscopy were 4.12 × 103 M− 1 at pH 4.0, 1.74 × 105 M− 1 at pH 6.0, and 5.98 × 105 M− 1 at pH 7.0. The binding constants at 298 K obtained from the fluorescence quenching method were 7.286 × 104 M− 1 at pH 4.0 and 1.45 7 × 105 M− 1 at pH 6.0. The thermodynamic parameters such as enthalpy change, entropy change, and free energy change were calculated, and the results indicated hydrogen bonds and van der Waals interactions played a major role in the binding reaction. The RLS experiment was performed to study the influence of porphyrin on the rPrPC aggregation at different pH values. The CD experiments were conducted to investigate the effects of porphyrin on the secondary structure and thermal stability of rPrPC. Finally, the comparison of SPR measurement and fluorescence quenching measurement was discussed.

Two mitochondria-targeted fluorescent probes (TPP- and TEA-BODIPY) were rationally designed and easily synthesized. These probes can specifically stain mitochondria in living cells with superior brightness, low cytotoxicity and high photostability, thus are quite promising as mitochondrial tracking probes.Two BODIPY-based fluorescent probes can specifically stain mitochondria with superior brightness, low cytotoxicity and high photostability.

An innovative trihexylsilylacetylene-containing BODIPY dye was designed and proved to be a highly selective, sensitive, and fast chromogenic and fluorescent chemodosimeter for fluorides.

Silver materials have been widely used as antimicrobial agents. Notably, silver nanoparticles have emerged as a new generation of nanoproducts for biomedical and environmental applications in recent years. However, ultrasmall silver nanoclusters (NCs) (∼2 nm) have rarely been used to kill bacteria and their antibacterial mechanisms have not yet been fully elucidated. Herein, we studied the antibacterial activities of bifunctional fluorescent DHLA-AgNCs against three types of bacteria. The results showed that DHLA-AgNCs exhibited excellent antibacterial activities against Gram-negative E. coli, which could efficiently inhibit the growth of E. coli DH 5α and E. coli DSM 4230 cells at a concentration of 15 and 10 μg mL−1, respectively. Meanwhile AgNCs demonstrated no apparent antibacterial activity against Gram-positive S. aureus. Then, the antibacterial mechanisms of AgNCs were systematically investigated. We found that AgNCs affected the growth of different E. coli strains in different ways. AgNCs inhibited the growth of E. coli DH 5α mainly through damaging the outer cellular membrane and permeating into the cells, followed by the antibacterial effect of the internalized AgNCs and released silver ions. AgNCs, however, inhibited the growth of E. coli DSM 4230 cells mainly through diffusing into E. coli DSM 4230 cells and damaging their respiratory chain. These results clearly indicated that different bacterial strains (e.g. different E. coli strains) should be taken into consideration in future studies. Our work facilitates further investigation of the design of new antibacterial silver nanomaterials with different sizes.