Silver-palladium bimetallic nanoparticles stabilized by elm pod polysaccharide with peroxidase-like properties for glutathione detection and photothermal anti-tumor ability.

Noble metal nanoparticles show good application prospects in biosensors and anti-tumor drug research. Herein, the near-spherical silver­palladium bimetallic nanoparticles supported by elm pod polysaccharide (EPP-AgPd1.5 NPs) were prepared by using the elm pod polysaccharide (EPP). EPP acts as a stabilizer and reducing agent due to its water solubility and weak reducing ability. The particle size of EPP-AgPd1.5 NPs was 33.6 ± 5.5 nm. In addition, EPP-AgPd1.5 NPs had peroxidase-like activity to catalyze 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized TMB by catalyzing H2O2 to OH. Based on the peroxidase-like activity of EPP-AgPd1.5 NPs, a method for detecting glutathione was established, and the detection limit and linear range of glutathione concentration were 0.279 µM and 0-400 µM, respectively. More importantly, the photothermal conversion efficiency of EPP-AgPd1.5 NPs reached 39.7 %, and their inhibition rate in HeLa cells reached 69.9 %. Silver­palladium bimetallic nanoparticles stabilized by EPP had good performance in glutathione detection and anti-tumor drugs.

Platinum Palladium Bimetallic Nanozymes Stabilized with Vancomycin for the Sensitive Colorimetric Determination of L-cysteine.

Many diseases in the human body are related to the level of L-cysteine. Therefore, it is crucial to establish an efficient, simple and sensitive platform for L-cysteine detection. In this work, we synthesized platinum palladium bimetallic nanoparticles (Van-Ptm/Pdn NPs) using vancomycin hydrochloride (Van) as a stabilizer, which exhibited high oxidase-like catalytic activity. In addition, the catalytic kinetics of the Van-Pt1/Pd1 NPs followed the typical Michaelis-Menten equation, exhibiting a strong affinity for 3,3',5,5'-tetramethylbenzidine substrates. More importantly, we developed a simple and effective strategy for the sensitive colorimetric detection of L-cysteine using biocompatible Van-Pt1/Pd1 NPs. The detection limit was low, at 0.07 µM, which was lower than the values for many previously reported enzyme-like detection systems. The colorimetric method of the L-cysteine assay had good selectivity. The established method for the detection of L-cysteine showed promise for biomedical analysis.

Zwitterionic Sulfhydryl Sulfobetaine Stabilized Platinum Nanoparticles for Enhanced Dopamine Detection and Antitumor Ability.

Herein, three kinds of molecules were used to modify the surface of platinum nanoparticles (Pt NPs) to tune their surface charge. Zwitterionic thiol-functionalized sulfobetaine (SH-SB) stabilized Pt NPs (SH-SB/Pt NPs) had the highest oxidase activity and peroxidase activity in the prepared platinum nanozymes due to the generation of reactive oxygen species. In addition, a colorimetric dopamine detection method was established based on the peroxidase activity of SH-SB/Pt NPs. This method had a wide range (0-120 µM), a low detection limit (0.244 µM), and high specificity. More importantly, SH-SB/Pt NPs displayed little hemolysis and good stability in the presence of proteins. SH-SB/Pt NPs demonstrated high cytotoxicity in vitro and good antitumor ability in vivo, which was attributed to the photothermal conversion ability of SH-SB/Pt NPs and the generation of reactive oxygen species in the acidic environment. The surface modification of nanozymes using zwitterionic molecules opens a new method to improve the catalytic activity and antitumor ability of nanozymes.

Green synthesis of Ag nanoparticles using elm pod polysaccharide for catalysis and bacteriostasis.

The green synthesis of silver nanoparticles (Ag NPs) for catalysis and biological applications has gained great interest. Natural elm pods are a type of food that possesses anti-inflammatory and pain-relieving effects. In this study, elm pod polysaccharide (EPP) was extracted from elm pods using hot water extraction for the first time. Biocompatible EPP-stabilized silver nanoparticles (EPP-Agn NPs) were prepared by using a green synthesis method. The EPP-Ag25 NPs had a hydrodynamic size of 40.9 nm and a highly negative surface charge of -27.4 mV. Furthermore, EPP-Ag25 NPs exhibited high catalytic activity for the reduction of 4-nitrophenol, and the catalytic reaction followed a pseudo-first order kinetic equation. More importantly, the inhibition rate of EPP-Ag25 NPs on Escherichia coli was 71 % when samples were treated with an 808 nm laser. Besides, EPP-Agn NPs effectively inhibited the proliferation of tumor cells irradiated by an 808 nm laser. The improved performance of EPP-Agn NPs was due to the good stability of EPP. Taken together, EPP-Agn NPs had good stability, catalytic activity, antibacterial and antitumor ability under laser irradiation. EPP is a good stabilizer for many nanoparticles which have broad applications in the field of catalysis and biomedicine in the future.

The Mn-modified porphyrin metal-organic framework with enhanced oxidase-like activity for sensitively colorimetric detection of glutathione.

The selective detection of glutathione (GSH) has been used as important colorimetric probe for human health. Herein, we used a facile method to synthesize manganese ions modified porphyrin metal-organic framework (PCN-224-Mn) with a size of 125.7 ± 14.2 nm and zeta potential of -3.9 ± 0.5 mV. We showed that PCN-224-Mn catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the absence of H2O2, resulting in a blue-colored oxidized TMB (oxTMB) that exhibits oxidase-like activity. Furthermore, a simple colorimetric detection method for GSH was developed based on the oxidase-like activity of PCN-224-Mn. This method shows wide linear detection range of 0.5-60 µM for GSH with a much lower detection limit of 0.233 µM. Finally, the recovery of colorimetric sensor of PCN-224-Mn suggests its great potential as a biosensor. As the catalytically active site, the manganese porphyrin unit plays a major role in the oxidase-like property and detection ability of PCN-224-Mn. Our data suggest that GSH detection method using PCN-224-Mn has great potential in multiple applications in the future.

Development of an Ultrasmall and Biocompatible Platinum Nanozyme Encapsulated by Zwitterionic Dendrimer for Highly Sensitive Detection of Glucose.

Many kinds of noble metal nanoparticles can mimic the peroxidase-like function of horseradish peroxidase, which results in their wide applications in bio-related detection and drug delivery. However, those metal nanoparticles usually have low stability and reduced catalytic activity in biological complex medium. Herein, a zwitterionic peroxidase-like enzyme has been developed, which has high stability in fibrinogen solutions and high sensitivity for glucose detection. Maleic anhydride, cysteamine, and zwitterionic peptide EKEKC (EK-5) were used to modify generation 5 poly(amido amine) dendrimers (G5 PAMAM) to prepare zwitterionic dendrimer G5MEKnC with nonfouling properties. Finally, the G5MEKnC-encapsulated platinum nanoparticles (Ptn-G5MEK50C) were prepared by entrapping the platinum nanoparticles (1.40 nm) in the catalytic centers in the interior of G5MEK50C. Pt55-G5MEK50C showed high stability in the buffer solution and the fibrinogen solution within 4 days. They also displayed high biocompatibility toward HeLa cells based on cytotoxicity results and morphological observations. Furthermore, the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine with H2O2 by Pt55-G5MEK50C followed the Michaelis-Menten equation, which confirmed their peroxidase-like properties. The catalytic mechanism was due to the generation of •OH from H2O2. More importantly, the peroxidase-like ability of Pt55-G5MEK50C was successfully used to establish a method for the determination of glucose concentration with a broad linear range of 1-2000 µM and a low detection limit of 0.1 µM. This method was highly accurate for the determination of glucose concentration in plasma. The zwitterionic dendrimer template enhanced the properties of Pt55-G5MEK50C. Taken together, a new kind of biocompatible nanozyme has been developed and successfully used for the sensitive detection of glucose in bio-related medium.

Biomineralized synthesis of palladium nanoflowers for photothermal treatment of cancer and wound healing.

Photothermal therapy uses photothermal agents (PTAs) to convert light energy to heat energy under near-infrared light to kill local tumors in cancer patients or speed up wound healing in diabetic patients. However, it is difficult to achieve high photothermal conversion efficiency for most of PTAs. Herein, daptomycin (Dap) micelles-stabilized palladium nanoflowers (Dap-PdNFs) were prepared for the first time. The palladium nanoflowers (PdNFs) inside of the Dap-PdNFs were 106 nm. The temperature of the Dap-PdNFs solution quickly rose from 26.8 °C to 52.0 °C within 10 min under irradiation with high photothermal conversion efficiency up to 38%. In addition, the cell viability of HeLa cells and HT-29 cells of Dap-PdNFs exceeded 95% in the absence of near-infrared light, indicating that Dap-PdNFs had good biocompatibility. Meanwhile, the inhibition rate of Dap-PdNFs on HeLa cells was as high as 71.2% under irradiation of 808 nm near-infrared light. More importantly, Dap-PdNFs had a good healing effect on wounds of diabetic mice under irradiation of 808 nm near-infrared light. In short, this research provides a facile method for the application of Dap-PdNFs in safe and efficient tumor treatment and wound healing.

Synthesis of gold nanoflowers stabilized with amphiphilic daptomycin for enhanced photothermal antitumor and antibacterial effects.

The development of effective agents for cancer therapy and inhibition of bacterial infection has drawn a great deal of interest. Photothermal therapy has been widely used for the thermal ablation of tumor cells. In addition, antibiotics have the ability to inhibit the growth of bacteria. Thus, the combination of photothermal therapy and antibiotics may be one of the methods to address the problem. Herein, it is the first time that daptomycin (Dap) micelles were used as the template and reducing agents to prepare stable daptomycin-gold nanoflowers (Dap-AunNFs) under mild conditions. The energy dispersive spectrometer (EDS) spectrum and X-ray diffraction (XRD) spectrum indicated that Dap-AunNFs were successfully prepared. When the molar ratio of HAuCl4 to Dap was 6, the gold nanoparticles inside of Dap-AunNFs were about 80 nm with flower-like shape. In addition, the photothermal conversion efficiency of Dap-Au6NFs was about 40%. More importantly, Dap-Au6NFs inhibited the growth of tumors and bacteria under the radiation of near-infrared light at 808 nm. The prepared Dap-Au6NFs could be used as photothermal antitumor and antibacterial agents in the future.

Biocompatible Dendrimer-Encapsulated Palladium Nanoparticles for Oxidation of Morin.

Development of highly efficient catalysts to expedite the degradation of organic dyes has been drawing great attention. The aggregation of catalysts reduces the accessibility of catalytic centers for organic dyes and therefore decreases their catalytic ability. Herein, we report a facile method to prepare highly biocompatible and stable dendrimer-encapsulated palladium nanoparticles (Pd n -G5MCI NPs), which exhibit high catalytic efficiency for oxidation of morin. The biocompatible dendrimers were prepared via surface modification of G5 polyamidoamine (G5 PAMAM) dendrimers using maleic anhydride and l-cysteine. Then, they were incubated with disodium tetrachloropalladate, followed by reduction using sodium borohydride to generate Pd n -G5MCI NPs. Transmission electron microscopy results demonstrated that palladium nanoparticles (Pd NPs) inside Pd n -G5MCI had small diameters (1.77-2.35 nm) and monodisperse states. Dynamic light scattering results confirmed that Pd n -G5MCI NPs had good dispersion and high stability in water. Furthermore, MTT results demonstrated that Pd n -G5MCI NPs had high biocompatibility. More importantly, Pd n -G5MCI NPs successfully catalyzed the decomposition of H2O2 to the hydroxyl radical (•OH), and the generated •OH quickly oxidized morin. This reaction kinetics followed pseudo-first-order kinetics. Apparent rate constant (k app) is an important criterion for evaluating the catalytic rate. The concentrations of Pd n -G5MCI NPs and H2O2 were positively correlated with k app, whereas the correlation between the concentration of morin and k app was negative. The prepared Pd n -G5MCI NPs have great potential to catalyze the degradation of organic dyes in bio-related systems in the future.

Enhanced glucose detection using dendrimer encapsulated gold nanoparticles benefiting from their zwitterionic surface.

The application of ultrasmall gold nanoparticles as enzyme mimics has been drawing great attention. Herein, we developed zwitterionic dendrimer encapsulated gold nanoparticles (Au-G5MC NPs) for highly sensitive and simple colorimetric detection of glucose. Au-G5MC NPs showed peroxidase-like property, which could efficiently catalyze oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2, producing a blue color product (oxTMB). This peroxidase-like reaction follows a typical Michaelis-Menten kinetics. The Km towards TMB exhibited a lower value (0.194 mM) than that of horseradish peroxidase (HRP, 0.434 mM). Furthermore, the peroxidase-like properties of Au-G5MC NPs enable colorimetric detection of the concentration of glucose with high selectivity. The linear concentration range of this method was from 14 µM to 166 µM with the detection limit down to 3.8 µM. More importantly, the detection was not interfered by proteins due to the single zwitterionic layer on the Au-G5MC NPs surface. These excellent properties are attributed to the ultrasmall size of gold nanoparticles and high stability of Au-G5MC NPs in complex medium. This catalytic system might have great potential applications for glucose detection in medical diagnostics and biochemistry in the future.

Enhanced biocompatibility of PAMAM dendrimers benefiting from tuning their surface charges.

The surface charge of dendrimers is one of the key factors that determine their use in nanomedicine. Generation 5 poly(amido amine) dendrimers (G5 PAMAM) encapsulating with fluorescein sodium were employed to study the method to tune surface charge. Firstly, the surface primary amines were reacted with maleic anhydride to introduce double bonds. Then, l-cysteine and cysteamine were conjugated to these double bonds via thiol-ene additions in water, respectively. The surface charges of modified G5 PAMAMs were successfully controlled by tuning the molar ratio of L-cysteine to cysteamine. The surface charges of the resulting modified G5 PAMAMs varied from -16.0 mV to -3.7 mV at physiological pH. In addition, they showed good compatibility with proteins and cells compared with G5 PAMAM. Modified G5 PAMAMs and fibrinogen could coexist in solution without generating noticeable aggregation, while G5 PAMAM induces significant aggregation, indicating these modifications can effectively reduce the interaction force between G5 PAMAM and proteins. Furthermore, modified G5 PAMAMs exhibited negligible hemolysis, while G5 PAMAM caused severe hemolysis. The cytotoxicity assay demonstrated that modified G5 PAMAMs exhibited very low cytotoxicity to both HUVEC cells and KB cells (>90% cell viability) at high concentrations up to 2 mg/mL. The cellular uptake of them was much less efficient compared with that of G5 PAMAM. Moreover, the intravenous injected modified G5 PAMAMs were excreted by kidney with a relatively little accumulation in liver, confirming their good biocompatibility in vivo. It is expected that the modified G5 PAMAMs could be an excellent candidate for contrast agent carriers in the future.

Highly water-soluble, pH sensitive and biocompatible PAMAM 'dendrizyme' to maintain catalytic activity in complex medium.

The dendrimer based synthetic mimetic enzyme has been drawing great attention. However, this mimetic enzyme is different from the natural enzymes, which are pH sensitive, biocompatible and keep their catalytic activity in biological complex medium. A single zwitterionic layer composed by primary amine and carboxyl groups may be a useful method to obtain these properties. Herein, we report a novel facile method to prepare a mimetic enzyme. The complexes of generation 5 poly(amido amine) dendrimers (G5 PAMAM) with free hemin (G5Hs) were modified by the maleic anhydride and cysteamine. Results showed that the mimetic enzymes (G5HMCs) had pH sensitivity and good stability by varying the pH from 4 to 9, while significant precipitation was observed for free hemin at pH5 after two days. The G5HMC (3:1) showed optimal catalytic activity at its isoelectric point. Furthermore, G5HMCs displayed excellent biocompatibility. The G5HMCs incubated with fibrinogen were stable for 24h, while G5Hs immediately formed large aggregates. G5HMC (3:1 2mg/mL) displayed little cytotoxicity with HeLa cells or A549 cells for 24h, while G5H (3:1) had serious cytotoxicity, which was also demonstrated by cell morphology observation. At last, G5HMCs fully preserved their catalytic activity in bovine serum albumin (BSA) solution compared with phosphate buffer saline (PBS) solution, while hemin decreased to 73.5-81.5% catalytic activity in BSA solution, which was caused by the less interaction with BSA for G5HMCs than free hemin. The surface functionalization schemes described in this report would represent a versatile method to prepare water-soluble, pH sensitive, biocompatible, and efficient artificial enzymes for biomedical related applications.