Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.

In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.

Regulating the morphology and structures of wet-chemical synthesized L10-FePtMn nanoparticles by applying magnetic fields.

We report an effective strategy to prepare highly ordered L10-FePt nanoparticles (NPs) by magnetic-field-assisted wet-chemical synthesis. The Mn element with high magnetic susceptibility was chosen for third-element addition, which is beneficial to reduce the required magnetic field strength for ordering transition. The evolution of morphology, ordering degree, and magnetic properties of the FePtMn nanomaterials in the synthesis process were systematically investigated. The attachment of spherical FePtMn NPs was facilitated by applying magnetic fields. The particle size was refined only when the magnetic field strength was as high as 6 T. The ordering degree and coercivity of NPs have been improved and reached the peak values when the magnetic field was 2 T, which can be easily achieved by using an ordinary electromagnet. Therefore, this work provides a feasible route for regulating the morphology and structural ordering of L10-phase ternary alloy NPs.

Novel Small-Molecule PD-L1 Inhibitor Induces PD-L1 Internalization and Optimizes the Immune Microenvironment.

Blocking the PD-1/PD-L1 interaction has become an important strategy for tumor therapy, which has shown outstanding therapeutic effects in clinical settings. However, unsatisfactory response rates and immune-related adverse effects limit the use of anti-PD1/PD-L1 antibodies. Here, we report the discovery and identification of S4-1, an innovative small-molecule inhibitor of PD-L1. In vitro, S4-1 effectively altered the PD-L1/PD-1 interaction, induced PD-L1 dimerization and internalization, improved its localization to endoplasmic reticulum, and thus enhanced the cytotoxicity of peripheral blood mononuclear cells toward tumor cells. In vivo, S4-1 significantly inhibited tumor growth in both lung and colorectal cancer models, particularly in colorectal cancer, where it led to complete clearance of a portion of the tumor cells. Furthermore, S4-1 induced T-cell activation and inversed the inhibitory tumor microenvironment, consistent with the PD-L1/PD-1 pathway blockade. These data support the continued evaluation of S4-1 as an alternative ICB therapeutic strategy.

Operating interfaces to synthesize L10-FePt@Bi-rich nanoparticles by modifying the heating process.

A facile strategy to operate interfaces when synthesizing L10-FePt@Bi-rich nanoparticles (NPs) has been proposed. Two interfaces are indispensable to obtain the high ordering L10-FePt structure. One is the mismatched interfaces between the initial γ-PtBi2 nuclei and the disordered fcc-FePt phase. The other is the in situ grown coherent interfaces between the L10-FePt and Bi-rich phases. Increasing the heating rates when the temperature rises from 120 °C to 310 °C benefits the formation of mismatched interfaces and improves the uniformity of phases and composition in NPs. Reducing the heating rate at higher temperature ensures sufficient time for Bi to diffuse across the coherent interface, which facilitates the disorder-order transition of L10-FePt NPs. This study provides a new perspective on operating interfaces during the wet-chemical synthesis process.

Polyethyleneimine Functionalized Mesoporous Magnetic Nanoparticles with Enhanced Antibacterial and Antibiofilm Activity in an Alternating Magnetic Field.

Despite a lot of research on the antibacterial effect of Fe3O4 nanoparticles, their interactions with biofilm matrix have not been well understood. The surface charge of nanoparticles mainly determines their ability to adhere on the biofilm. In this work, negatively charged Fe3O4 nanoparticles were synthesized via a trisodium citrate-assisted solvothermal method and then the surfaces were functionalized using polyethyleneimine (PEI) to obtain positively charged Fe3O4 nanoparticles. The antibacterial and antibiofilm activities of both negatively and positively charged Fe3O4 nanoparticles in an alternating magnetic field were then systematically investigated. The positively charged Fe3O4 nanoparticles showed a strong self-adsorbed attachment ability to the planktonic and sessile cells, resulting in a better antibacterial activity and enhanced biofilm eradication performance compared to the conventional Fe3O4 nanoparticles with negative charges. Fe3O4@PEI nanoparticles produced physical stress and thermal damage in response to an alternating magnetic field, inducing the accumulation of intracellular reactive oxygen species into live bacterial cells, bacterial membrane damage, and biofilm dispersion. Utilizing an alternating magnetic field along with positively charged nanoparticles leads to a synergistic antibacterial approach to improve the antibiofilm performance of magnetic nanoparticles.

Topology, tissue distribution, and transcriptional level of SLC34s in response to Pi and pH in grass carp Ctenopharyngodon idella.

In the present study, two new SLC34 family members, named slc34a1b and slc34a2a, were isolated and characterized from grass carp Ctenopharyngodon idella. Topology, tissue distribution, and transcriptional response to phosphorus (Pi) and pH were compared among three members of SLC34 family (slc34a1b, slc34a2a, and slc34a2b) in grass carp. The length of validated cDNAs of grass carp slc34a1b and slc34a2a was 1494 bp and 1902 bp, and these two cDNAs encoded 497 and 633 amino acid residues, respectively. The domain analysis showed that three SLC34 members of grass carp contain architecture similar to that in mammals. Moreover, the mRNA of three slc34s was widely expressed in nine tissues (heart, brain, intestine, kidney, liver, muscle, gill, spleen, and skin), but at various levels. Our results revealed that 6 mM and 9 mM Pi incubation significantly reduced the mRNA expression of three slc34s in both CIK and L8824 cell lines from grass carp. The expression of slc34a1b was decreased in the CIK cells, but not in the L8824 cells after 3 mM Pi incubation. In CIK cells, 3 mM Pi incubation downregulated the expression of slc34a1b and slc34a2a, but not slc34a2b. In addition, the expression of three slc34s was significantly reduced at acidic pH in the CIK cells. Taken together, we characterized three SLC34 family members, revealed their specific distribution among different tissues, and elucidated their transcriptional responses to Pi and pH in two cell lines from grass carp. Our findings provide an insight into the physiological function of three SLC34s in fish.

Effects of high magnetic field annealing on FePt nanoparticles with shape-anisotropy and element-distribution-anisotropy.

The concave-cube FePt nanoparticles (NPs) with shape-anisotropy and element-distribution-anisotropy were annealed under a high magnetic field (HMF). The NPs underwent spheroidization and phase transformation during the annealing process. The HMF hardly affected the spheroidizing process of NPs, but obviously facilitated the disorder-order transition of the L10-phase. The L10-phase content, ordering degree, and the coercivity of annealed NPs increased with enhancing the HMF strength. Those results indicated that the nucleation of the L10-phase and ordering diffusion of Fe/Pt atoms were promoted by the HMF.

Influence of a Reduction Process on the Phase Component and Magnetic Properties of NdFeB Magnetic Nanoparticles.

NdFeB magnetic nanoparticles with a main phase of Nd2Fe14B have successfully been synthesized. The preparation includes the following processes. First, the NdFeB intermediate was synthesized by a wet-chemical method. The NdFeB intermediate was annealed at 800 °C, which resulted in the formation of an NdFeB oxide. Then, the NdFeB oxide was reduced into NdFeB nanoparticles by a second-step reduction annealing with a CaH2 reductant. The second-step reduction annealing temperature was a key factor in preparing the NdFeB nanoparticles. A lower reduction temperature of 900 °C could not completely reduce the NdFeB oxide into Nd2Fe14B. There were some residual unreduced nonmagnetic phases in the prepared materials, which resulted in obvious decreases of coercivity. A sufficiently high second-stage reduction temperature resulted in an increased reduction, and more of the Nd2Fe14B phase could be obtained. In this work, nanoparticles with a uniform morphology and an increased Nd2Fe14B phase could be obtained at an optimum reduction temperature of 940 °C, achieving a high coercivity of 5.4 kOe.

Tailoring the shape and size of wet-chemical synthesized FePt nanoparticles by controlling nucleation and growth with a high magnetic field.

A 6 Tesla high magnetic field (HMF) was separately introduced into the nucleation stage and growth stage and into both stages during the wet-chemical synthesis of FePt nanoparticles. The HMF refined particle sizes and increased the nucleation rate in the nucleation stage and tailored shapes and refined sizes in the growth stage. Extension of nucleation time increased the nucleation rate more than that of the HMF, which increasing was higher enough to tailor the shapes of FePt nanoparticles. Controlling nucleation is a feasible strategy to tailor the shapes and sizes of wet-chemical synthesized nanoparticles.

Hyperbranched Co2P nanocrystals with 3D morphology for hydrogen generation in both alkaline and acidic media.

Hyperbranched Co2P nanocrystals with three-dimensional structure have successfully been synthesized by a facile one-step wet-chemical method. The hyperbranched Co2P are consisted of a large number of nanofilaments. The crystal splitting should be responsible for the formation of this structure. Catalytic performances measurements toward hydrogen evolution reaction for the obtained hyperbranched Co2P nanocrystals demonstrate a small overpotential of 100 mV at current density of 10 mA cm-2, with a Tafel slope of 67 mV dec-1 in 1 M KOH. Durability tests show that slight catalytic activity fading occurs after 2000 CV cycles or 22 h chronoamperometric testing. In addition, the hyperbranched Co2P also perform well in 0.5 M H2SO4 with a low overpotential of 107 mV at 10 mA cm-2 and a Tafel slope of 69 mV dec-1. This facile method provides a strategy for the preparation of low-cost metal phosphide electrocatalysts for hydrogen evolution in both alkaline and acidic media.

Evolution of the phases and the polishing performance of ceria-based compounds synthesized by a facile calcination method.

Ceria-based compounds with additions of La and F (CLF compounds) were prepared by using industrial-grade fluorinated lanthanum cerium carbonate as a precursor via a facile calcination method. The evolution of phase structures of the compounds during preparation and the relationship between the structure and the polishing performance were investigated. The compounds consist of three phases: CeO2, LaOF, and LaF3. The phase component could be controlled by tuning the calcination process. A higher degree of fluorination and a higher calcination temperature led to the formation of more LaOF and less LaF3 phases. The LaOF phase performs a higher stock removal rate. The best polishing efficiency was achieved with LaOF phase ratio around 18%. Intermetallic LaF3 is a low-hardness phase and is easily crushed during polishing, which lowers the removal rate and shortens the useful life of the polishing powder.

Facile liquid-assisted one-step sintering synthesis of superfine L10-FePt nanoparticles.

A liquid-assisted one-step sintering method was proposed for the synthesis of L10-FePt superfine nanoparticles. The liquid assisted Fe and Pt precursors were homogeneously deposited on NaCl media, which facilitated the nucleation rates, obviously reduced the particle size and promoted the orderly transformation. Through optimizing the sintering parameters, superfine L10-FePt nanoparticles (about 7 nm, TEM) with coercivity as high as 2.29 T were obtained. This research highlights the feasibility of synthesizing L10-FePt nanoparticles with superfine sizes and ultra-high coercivity.

Evolution of microstructure and formation mechanism of Nd-Fe-B nanoparticles prepared by low energy consumption chemical method.

Nd2Fe14B nanoparticles were successfully prepared by using a low-energy chemical method. The microscopic characteristics and formation mechanisms of the phases were investigated at each stage during the preparation of Nd-Fe-B nanoparticles. The Nd-Fe-B intermediates, Nd-Fe-B oxides and reduced Nd-Fe-B nanoparticles were detected and analyzed by using TEM, STEM, XRD, SEM, VSM and Rietveld calculations. The results showed that the intermediate of Nd-Fe-B consisted of Fe3O4 and Nd and Fe elements surrounded by nitrile organic compounds. The Nd-Fe-B oxide was composed of NdFeO3 (48.619 wt%), NdBO3 (31.480 wt%) and α-Fe (19.901 wt%), which was formed by the reaction among Nd, Fe3O4 and B2O3. NdFeO3 and NdBO3 exhibited a perovskite-like lamellar structure, and the grain size was smaller than that of α-Fe. Nd-Fe-B particles were mainly composed of Nd2Fe14B and α-Fe phases. The small particles of NdFeO3 and NdBO3 and the interstitial position between oxide particles and α-Fe were more favorable for the formation of Nd2Fe14B particles. At the same time, the surface of α-Fe particles can also diffuse to form Nd2Fe14B nanoparticles. The coercivity of Nd-Fe-B particles was 5.79 kOe and the saturation magnetization was 63.135 emu g-1.

Synergetic Effect of Dy2O3 and Ca Co-Dopants towards Enhanced Coercivity of Rare Earth Abundant RE-Fe-B Magnets.

Low coercivity is the main disadvantage of RE-Fe-B permanent magnets containing highly abundant rare earths (RE: La, Ce) from the application point of view, even though they exhibit many cost and resource advantages. In this work, an industrial mixed rare earth alloy (RE100 = La30.6Ce50.2Pr6.4Nd12.8) with a high amount of the more abundant elements was adopted to fabricate RE-Fe-B permanent magnets by means of mechanical alloying accompanied by post-annealing. A synergetic effect towards enhancing the coercivity was observed after co-doping with Dy2O3 and Ca, with the coercivity increasing from 2.44 kOe to 11.43 kOe for co-dopant percentages of 7 wt.% Dy2O3 + 2.3 wt.% Ca. Through analysis of the phase constituents and microstructure, it was determined that part of the Dy atoms entered the matrix of RE2Fe14B phase to enhance the magnetocrystalline anisotropy; due to the reductive effect of Ca on Dy2O3, nanocrystals of Dy-rich RE2Fe14B were present throughout the matrix, which could increase the resistance to domain wall movement. These are the dominant factors behind the improvement of the coercivity of the RE-Fe-B magnets with highly abundant RE elements.

Post-treatment Method for the Synthesis of Monodisperse Binary FePt-Fe3O4 Nanoparticles.

To obtain the optimal 1:1 composition of FePt alloy nanomaterials by polyol synthesis, the iron precursor (iron pentacarbonyl, Fe(CO)5) must be used in excess, because the Fe(CO)5 exists in the vapor phase at the typical temperatures used for FePt synthesis and cannot be consumed completely. Fabrication of Fe3O4 nanoparticles by consuming the excess iron precursor was an effective strategy to make full use of the iron precursor. In this paper, a facile post-treatment method was applied to consume the excess iron, which was oxidized to Fe3O4 after post-treatment at 150 and 200 °C, and a monodisperse binary FePt-Fe3O4 nanoparticle system was generated. The post-treatment method did not affect the crystal structure, grain size, or composition of the FePt nanoparticles. However, the content and grain size of the fcc-Fe3O4 nanoparticles can be increased simply by increasing the post-treatment temperature from 150 to 200 °C.

Enzyme-free amperometric sensing of hydrogen peroxide and glucose at a hierarchical Cu2O modified electrode.

In this paper, an enzyme-free amperometric electrochemical sensor was fabricated by casting Nafion-impregnated Cu(2)O particles onto a glassy carbon electrode. A dual dependence of peak current on sweeping rate, which can be attributed for the accumulation of reaction products, was observed on the sensor. Electrochemical analysis of the particulate Cu(2)O for detecting H(2)O(2) and glucose is described, showing remarkable sensitivity in both cases. The estimated detection limits and sensitivities for H(2)O(2) (0.0039 µM, 52.3 mA mM(-1) cm(-2)) and glucose (47.2 µM, 0.19 mA mM(-1) cm(-2)) suggest that the response for H(2)O(2) detection was much higher than for glucose detection. Electron microscopy observation suggested that the hierarchical structures of Cu(2)O resulting from self-assembly of nanocrystals are responsible for the specific electrochemical properties.