Research Status of Dendrimer Micelles in Tumor Therapy for Drug Delivery.

Dendrimers are a family of polymers with highly branched structure, well-defined composition, and extensive functional groups, which have attracted great attention in biomedical applications. Micelles formed by dendrimers are ideal nanocarriers for delivering anticancer agents due to the explicit study of their characteristics of particle size, charge, and biological properties such as toxicity, blood circulation time, biodistribution, and cellular internalization. Here, the classification, preparation, and structure of dendrimer micelles are reviewed, and the specific functional groups modified on the surface of dendrimers for tumor active targeting, stimuli-responsive drug release, reduced toxicity, and prolonged blood circulation time are discussed. In addition, their applications are summarized as various platforms for biomedical applications related to cancer therapy including drug delivery, gene transfection, nano-contrast for imaging, and combined therapy. Other applications such as tissue engineering and biosensor are also involved. Finally, the possible challenges and perspectives of dendrimer micelles for their further applications are discussed.

Yolk-shell Co3 O4 @Fe3 O4 /C Nanocomposites as a Heterogeneous Fenton-like Catalyst for Organic Dye Removal.

The yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites with Co3 O4 as the core, Fe3 O4 /C as the shell, and a cavity structure were synthesized by the hard template method. The physical and chemical properties of the composites were characterized by SEM, TEM, XRD, TGA, XPS, BET, and VSM. The specific surface area of yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites is 175.9 m2  g-1 , showing superparamagnetic properties. The yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites were used as heterogeneous Fenton catalysts to activate peroxymonosulfate (PMS) to degrade MB, which showed high catalytic degradation performance. The degradation rate of MB reached 100 % within 30 min under the circumstances of the yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites dosage of 0.1 g L-1 , the PMS dosage of 1.0 g L-1 , the initial MB concentration of 100 mg L-1 , an initial pH of 5.5, and a temperature of 30±2 °C. The enhanced catalytic performance of the yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites can be attributed to the synergistic effect of the two catalytically active materials and the middle cavity. The effects of different operating parameters and co-existing anion species on MB degradation were also investigated. Electron paramagnetic resonance (EPR) analysis and quenching experiments confirmed that the formation of SO4 ⋅- in the yolk-shell Co3 O4 @Fe3 O4 /C/PMS system contributes to MB degradation. In addition, yolk-shell Co3 O4 @Fe3 O4 /C nanocomposites can be easily separated from the pollutant solution under the action of an external magnetic field, and the degradation rate of MB can still reach 98 % after five cycles, indicating that it has good stability and reusability and has broad application prospects in the field of water purification.

Recent development and application of membrane chromatography.

Membrane chromatography is mainly used for the separation and purification of proteins and biological macromolecules in the downstream processing process, also applications in sewage disposal. Membrane chromatography is recognized as an effective alternative to column chromatography because it significantly improves chromatography from affinity, hydrophobicity, and ion exchange; the development status of membrane chromatography in membrane matrix and membrane equipment is thoroughly discussed, and the applications of protein capture and intermediate purification, virus, monoclonal antibody purification, water treatment, and others are summarized. This review will provide value for the exploration and potential application of membrane chromatography.

An all-dielectric metasurface based on Fano resonance with tunable dual-peak insensitive polarization for high-performance refractive index sensing.

A symmetric all-dielectric metasurface based on silicon and GaAs is proposed and numerically studied. In the mid-infrared region, two Fano resonant peaks with a reflectance exceeding 90% are observed. By altering the geometric parameters of the metasurface, the wavelength location and quality factor (Q-factor) of the resonant peaks can be tuned. The highest Q-factors can be 9609.67 and 3476.33, respectively. The proposed metasurface structure for optical refractive index sensing shows high performance and is insensitive to the plane wave's polarization state. In the refractive index range of 1.00 to 1.10, the highest sensitivity and figure of merit (FoM) are 1901.34 nm RIU-1 and 2492.04 RIU-1, respectively. The highest sensitivity is 2248.57 nm RIU-1 and FoM is 977.64 RIU-1 in the refractive index range of 1.30 to 1.40. These research results will help improve and innovate related sensing technologies and devices.

Dual receptor NIR-II organic nanoparticles for multimodal imaging guided tumor photothermal therapy.

The second near-infrared (NIR-II) fluorescence imaging has attracted continuous attention due to its excellent penetration depth and high spatial resolution. Compared with other fluorophores, NIR-II fluorophores, especially NIR-II organic small molecule fluorophores, are favored because of their controllable structure and good biocompatibility. In this study, we designed and synthesized an S-D-A-D-S type small molecule FEA. However, a new molecule was accidentally obtained in the process of synthesis, which was proved to be a double receptor (A-A) type small molecule, namely S-D-A-A-D-S type organic small molecule FEAA. Compared with FEA molecules, FEAA exhibits superior fluorescence performance and can effectively prevent fluorescence quenching. The fluorescence emission of its nanoparticles (NPs) reaches 1109 nm, extends to about 1400 nm, and has a Stokes shift of up to 472 nm. Subsequently, we realized fluorescence/photoacoustic dual-mode imaging (FI/PAI) of nude mouse liver, and finally effectively ablated 4T1 tumor by photothermal therapy (PTT). In general, FEAA NPs exhibit good fluorescence, photoacoustic, and photothermal effects, and are an excellent multifunctional NIR-II organic small molecule fluorophore. As far as we know, there are few reports on A-A type organic small molecules, most of which are cyanines or D-A-D type structures. Therefore, this study has good exploratory significance and reference value for the discovery of NIR-II fluorophores.

Analysis of proteins and chiral drugs based on vancomycin covalent capillary electrophoretic coating.

Vancomycin is an amphoteric glycopeptide molecule, and its group diversity and chiral active sites provide a potential basis for its application in chromatographic analysis. In this article, using photosensitive diazo resin (DR) as the coupling agent, vancomycin is modified on the inner wall of the capillary to construct a capillary coating separation system. The highlight of the coated capillary is that it has both anti-protein adsorption and chiral separation properties. Compared with the bare capillary or non-covalently bonded DR/vancomycin-coated capillary, it can not only achieve the separation of four mixed proteins of lysozyme (Lys), bovine serum albumin (BSA), myoglobin (Mb), and ribonuclease A (RNase A), but also shows excellent performance in chiral drugs. The coated capillary effectively solves the problems of low efficiency of the separation column and high sample loss and provides ideas for the development of coated capillaries in the future.

A novel M2Ga2GeO7:N3+(M = Ca, Ba, Sr; N = Cr, Nd, Er) sub-micron phosphor with multiband NIR emissions: preparation, structure, properties, and LEDs.

Near-infrared (NIR) emission materials can be widely applied in various fields, such as food detection, imaging, treatment, electronic products. With the trend of miniaturization of equipment, smaller materials are needed. In this work, we successfully synthesized a series of M2Ga2GeO7:N3+(M = Ca, Ba, Sr; N = Cr, Nd, Er) samples and then focused on the study of Nd3+doped Sr2Ga2GeO7(SGGO). A series of SGGO:xNd3+sub-micron phosphors were prepared via a microwave-assisted sol-gel process combined with subsequent calcination at 750 ℃, and the structural information and luminescent properties were systematically studied. SGGO is a representative tetragonal crystal and belonging to the space group of P4¯21m (113). The Nd3+ions occupy eight-coordinated Sr2+sites in the crystal lattice. From SEM analysis, the average particle size distribution is 219.7 ± 41.4 nm. The sub-micron phosphors have rich excitation spectra ranging from 350 nm to 850 nm and can produce multiband NIR emissions of 1331, 1056, and 905 nm when excited by ultraviolet and NIR light. The maximum emission intensity was obtained by optimizing the doping ratio of Nd3+ions. A commercial chip was then utilized to fabricate light-emitting diodes (LEDs) to verify its application potential in NIR-II mini-LEDs. Compared with blue light LEDs, the as-prepared LEDs had good imaging penetration depth and could be clearly observed under 10 mm of chicken breast coverage. The maximum imaging penetration depth can be 33 mm.

Regioselective Synthesis, Crystallographic Characterization, and Electrochemical Properties of Pyrazole- and Pyrrole-Ring-Fused Derivatives of Y2 @C3v (8)-C82.

Chemical modification of endohedral metallofullerenes (EMFs) is an efficient strategy to realize their ultimate applications in many fields. Herein, we report the highly regioselective and quantitative mono-formation of pyrazole- and pyrrole-ring-fused derivatives of the prototypical di-EMF Y2 @C3v (8)-C82 , that is, Y2 @C3v (8)-C82 (C13 N2 H10 ) and Y2 @C3v (8)-C82 (C9 NH11 ), from the respective 1,3-dipolar reactions with either diphenylnitrilimine or N-benzylazomethine ylide, without the formation of any bis- or multi-adducts. Crystallographic results unambiguously reveal that only one [6,6]-bond out of the twenty-five different types of nonequivalent C-C bonds of Y2 @C3v (8)-C82 is involved in the 1,3-dipolar reactions. Our theoretical results rationalize that the remarkably high regioselectivity and the quantitative formation of mono-adducts are direct results from the anisotropic distribution of π-electron density on the C3v (8)-C82 cage and the local strain of the cage carbon atoms as well. Interestingly, electrochemical and theoretical studies demonstrate that the reversibility of the redox processes, in particular the reversibility of the reductive processes of Y2 @C3v (8)-C82 , has been markedly altered upon exohedral functionalization, but the oxidative process was less influenced, indicating that the oxidation is mainly influenced by the internal Y2 cluster, whereas the reduction is primarily associated with the fullerene cage. The pyrazole and pyrrole-fused derivatives may find potential applications as organic photovoltaic materials and biological reagents.

Dynamic Covalent C═C Bond, Cross-Linked, Injectable, and Self-Healable Hydrogels via Knoevenagel Condensation.

Hydrogels have a wide range of applications in the fields of biomedicine, flexible electronics, and bionics. In this study, injectable and self-healable hydrogels were first prepared based on a dynamic covalent C═C bond formed via the Knoevenagel condensation reaction between poly(ethylene glycol) dicyanoacetate and water-soluble poly(vanillin acrylate). Three kinds of catalysts (phosphate buffer, zeolitic imidazolate framework-8, and tertiary amine) were used in Knoevenagel condensation for preparing hydrogels. All hydrogels in this study could be formed in situ, and their gelation time ranged from seconds to minutes. The properties and application of hydrogels could be customized according to the type of catalyst employed. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) results indicated that all the components and hydrogels exhibited low toxicity, and the hydrogels could be used as 3D cell culture scaffolds. Because of the dynamic covalent C═C bond formed by Knoevenagel condensation, the resultant hydrogels were found to be dynamic and showed good self-healing properties. This work presents a new dynamic covalent chemistry for the preparation of self-healable materials.

Tumor microenvironment-responsive polymer with chlorin e6 to interface hollow mesoporous silica nanoparticles-loaded oxygen supply factor for boosted photodynamic therapy.

Cancer treatment has always been a big problem for people. With the application of photodynamic therapy, the problem has been alleviated. However, the problem of tumor hypoxia affecting photodynamic therapy has been waiting to be resolved. Therefore, we report here that a redox nanocarrier (called RN) is prepared by hollow mesoporous silica sphere (HMSNs) and a redox-responsive polymer ligand. The nanocarrier is loaded with metformin and catalase, and the polymer is linked to the photosensitizer chlorin e6 (Ce6). Metformin inhibits the mitochondrial respiration of cancer cells, reducing the activity of cancer cells and increasing the oxygen concentration required for photodynamic therapy. Not only the effect of photodynamic therapy is enhanced, but also the effect of chemotherapy is increased to achieve super additive treatment. These RNs exhibit not only low cytotoxicity but also high biocompatibility in vitro experiments. In vitro Ce6 release studies have shown a higher release in the presence of glutathione (GSH). Confocal microscopy can further indicate that the nanoparticles are carried to the area around the nucleus of the cancer cells. In addition, treatment with a mouse tumor model demonstrated that RN has an effective therapeutic effect on tumors.

Biomedical application of manganese dioxide nanomaterials.

Manganese dioxide nanomaterial is a new type of inorganic nanomaterial offering numerous advantages: simple preparation, low cost, and environmental friendliness. This review summarizes the traditional and novel synthetic methods for manganese dioxide nanomaterials and mainly discusses their potential in biomedical applications. Manganese dioxide nanomaterials are mainly used as drug carriers in tumor therapy. In recent years, the construction of multifunctional nano-platforms using manganese dioxide has gradually improved. The main mechanism is that manganese dioxide nanomaterials can combine with reactive oxygen species in the tumor microenvironment to alleviate tumor hypoxia. Manganese dioxide has also been used to quench fluorescent carbon dots in fluorescent probes. Based on the oxidation ability and catalytic activity of MnO2, MnO2 nanosheets are widely used to build biosensors. New research shows that manganese dioxide nanomaterials also have great potential in gene therapy and nuclear magnetic imaging.

Organic Semiconductors for Photothermal Therapy and Photoacoustic Imaging.

In recent years, semiconducting polymer nanoparticles (SPNs) have been attracting considerable attention because of their outstanding characteristics such as higher light and thermal stability. They are widely used in fields of biomedicine such as photoacoustic (PA) imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). PAI, a new imaging modality based on PA effects, shows great promise in biomedical applications. SPNs that display strong optical absorbance in the visible and near-infrared (NIR) regions can be promising candidates for in vivo PTT and PAI. Here we introduce the preparation of organic conjugated polymer fluorescent nanoparticles in the aqueous phase. We then discuss the application of water-dispersible conjugated polymer nanoparticles in PA and PTT. Finally, we discuss the opportunities and challenges for the development of organic conjugated polymer nanoparticles.

Conjugated-Polymer-Based Nanoparticles with Efficient NIR-II Fluorescent, Photoacoustic and Photothermal Performance.

Fluorescence imaging (FI) and photoacoustic imaging (PA) play important roles in the real-time assessment of cell-based therapies. However, the limitations of conventional organic fluorescence contrast agents and the narrow range of the emission wavelength in the first near-infrared (NIR-I) window (750-900 nm) hamper applications of fluorescence imaging in living subjects. Herein, we report the design and synthesis of a short-wave infrared FI contrast agent and PA contrast agent based on a conjugated polymer-poly{2,5-bis[(5-thiophen-2-yl)methylene]-3,6-bis(2-octyldodecyl)-2,5-dihydropyrazine}-and its use to construct multifunctional nanoparticles to simplify photothermal therapy.

Ho2O@C84: Crystallographic Evidence Showing Linear Metallic Oxide Cluster Encapsulated in IPR Fullerene Cage of D2d(51591)-C84.

Fullerene C84 is the third-most-abundant species after C60 and C70. In the past decade, a variety of C84-based clusterfullerenes have been well-studied experimentally, which otherwise do not include oxide clusterfullerenes (OCFs). In this work, we report a comprehensive inspection of Ho2O@C84, including its mass, spectroscopic, crystallographic, electrochemical (EC), and density functional theory (DFT) studies. Importantly, crystallographic data reveal an IPR cage of D2d(51591)-C84 with a linear endohedral Ho-O-Ho cluster, indicating that the compression effect of the C84 cage is less pronounced compared to that of a smaller cage. The experimentally observed structure is confirmed by DFT computations, which also verify its superior stability. Further studies suggest that Ho2O@C84 has reduced EC and HOMO-LUMO gaps compared to those of empty species, again demonstrating the effect of cluster encapsulation.

Ho2O@C74: Ho2O Cluster Expands within a Small Non-IPR Fullerene Cage of C2(13333)-C74.

Steering the cluster configuration inside a fullerene cage has been one of most interesting topics in the field of fullerenes, since the physical property of a cluster fullerene may be modified accordingly. It has been well-recognized that the cluster configuration can be tuned via altering the cage size. Typically, the carbide cluster and the oxide cluster are experimentally seen to be curled up within a small fullerene cage whereas they are expanded in a large cage. In this work, a new oxide cluster fullerene Ho2O@ C2(13333)-C74 is prepared and isolated. The single-crystal X-ray diffraction (XRD) study reveals that the Ho2O cluster, however, expands within the small non-IPR cage of C2(13333)-C74 with a Ho-O-Ho angle of >170°, indicating that cluster configuration is highly related to the cage shape and cage structure as well. The DFT computation demonstrates that the cluster-to-cage electron-transfer obviously enhances the aromaticity of the motif containing the fused-pentagon pair and hence stabilizes the non-IPR cage of C2(13333)-C74. In addition, the electrochemical and magnetic properties of Ho2O@ C2(13333)-C74 are studied to further investigate the effect of endohedral Ho2O cluster.

Multifunctional Fe3O4@C-based nanoparticles coupling optical/MRI imaging and pH/photothermal controllable drug release as efficient anti-cancer drug delivery platforms.

Multifunctional nanomedicines featuring high drug loading capacity, controllable drug release and real-time self-monitoring are attracting increasing attention due to their potential to improve cancer therapeutic efficacy. Herein, a new kind of Fe3O4@C-based nanoparticles modified with isoreticular metal organic frameworks (IRMOF-3), folic acid (FA) and detachable polyethylene glycol (PEG) under tumor microenvironment was developed. The core-shell structured Fe3O4@C was synthesized via the one-pot solvothermal reaction and the IRMOF-3 layers were coated on the outer shell of Fe3O4@C through layer-by-layer coating method. The FA and PEG were conjugated on the surface of nanoparticles by reacting with the amine groups provided by IRMOF-3. The as-synthesized nanoparticles showed stable photothermal effect, superparamagnetic properties and blue fluorescence characteristic under 360 nm irradiation. The in vitro experiments showed that the drug loaded nanoparticles exhibit pH-dependent drug release property, and PEGylation was proved effective in suppressing burst drug release (only 8.0% of drugs were released within 95 h). The confocal laser scanning microscopy study revealed that the as-synthesized nanoparticles could serve as a cell imaging agent and the cell internalization can be significantly enhanced after FA modified. The IRMOF-3 modified nanoparticles showed negligible cytotoxicity and the drug loaded nanoparticles showed pH/photothermal-stimuli enhanced cytotoxicity in vitro. It is believed that the present smart drug delivery platforms will hold great potential in imaging guided drug delivery and cancer therapy.

Construction of Dimeric Drug-Loaded Polymeric Micelles with High Loading Efficiency for Cancer Therapy.

Polymeric micelles (PMs) have been applied widely to transport hydrophobic drugs to tumor sites for cancer treatment. However, the low load efficiency of the drug in the PMs significantly reduces the therapeutic efficiency. We report here that disulfide-linked camptothecin (CPT) as a kind of dimeric drug can be effectively embedded in the core of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) PMs for improving drug-loading efficiency, and PEG can be used as a hydrophilic shell. Moreover, the dimeric CPT-loaded PCL-PEG-PCL PMs exhibited excellent solubility in phosphate-buffered saline (PBS) media and significant cytotoxicity to cancer cells.

Recent Progress in Fluorescence Imaging of the Near-Infrared†II Window.

Near-infrared (NIR) fluorescent materials are considered to be the most promising labeling reagents for sensitive determination and biological imaging due to the advantages of lower background noise, deeper penetrating capacity, and less destructive effects on the biomatrix over those of UV and visible fluorophores. In the past decade, advances in biomedical fluorescence imaging in the NIR region have focused on the traditional NIR window (NIR-I; λ=700-900 nm), and have recently been extended to the second NIR window (NIR-II; λ=1000-1700 nm). In vivo NIR-II fluorescence imaging outperforms imaging in the NIR-I window as a result of further reduced absorption, tissue autofluorescence, and scattering. In this review, the applications of four types of NIR-II fluorescent materials, organic fluorophores, quantum dots, rare-earth compounds, and single-walled carbon nanotubes, are summarized and future trends are discussed. Some methods to enhance the NIR-II fluorescence quantum yield are also proposed.

Preparation of pocket shaped microfiltration membranes with binary porous structures.

Highly permeable pocket-shaped microfiltration membranes with binary porous structures, which are composed of brominated poly(2,6-dimethyl-1,4-phenylene oxide) (BPPO), were prepared on needles by breath figure (BF) and colloidal crystal template (CCT) methods. In colloidal crystal templates, the membrane pore size in the bottom layer was adjusted by SiO2 microsphere diameter in the colloidal crystal template, while that in the top layer was adjusted by changing the BPPO concentration. The permeability of the binary porous membrane prepared by BF and CCT methods was higher than that of membranes only prepared by the BF method. Due to high permeability and antifouling properties, the pocket shaped binary porous membrane was connected to a syringe and used as a filter film in microfiltration and sample preparation fields.

A covalent capillary coating of diazoresin and polyglycerol dendrimer for protein analysis using capillary electrophoresis.

Overcoming proteins adsorption on the inner surface of capillary has attracted increasing attention recently. By using the unique photochemistry reaction of diazoresin (DR), a new covalent capillary coating was prepared on the fused-silica capillary through layer-by-layer self-assembly of DR with polyglycerol (PG) dendrimer. The separation performance of covalently DR/PG-dendrimer coated capillary noticeably exceeded the bare capillary and the noncovalently linked DR/PG-dendrimer capillary. A baseline separation of lysozyme, myoglobin, bovine serum albumin, and ribonuclease A was achieved using CE within 20 min. Besides, the covalently linked DR/PG-dendrimer coating has the remarkable stability and reproducibility. Especially, compared with the traditional method which use highly toxic and moisture-sensitive silane coupling agent, this method seems to be a simple and environmental friendly way to prepare the covalently coated capillaries for CE.