Chelated Metal-Organic Frameworks for Improved the Performance of High-Nickel Cathodes in Lithium-Ion Batteries.

Lithium-ion batteries have gained widespread use in various applications, including portable devices, electric vehicles, and energy storage systems. High Ni cathode, LiNixCoyMnzO2 (NCM, x ≥ 0.8, x + y + z = 1), have garnered significant attention owing to their high energy density. However, the limited lithium-ion transfer rate and transition metal cross-talk to anode pose obstacles to further improvement of electrochemical performance. To tackle these challenges, metal-organic frameworks (MOFs) with chelating agents are employed as additive materials for electrode. MOFs with chelating agents offer three key attributes: (1) Effective mitigation of transition metal cross-talk to the anode, (2) Partial desolvation of Li+ ions through MOF pores, and (3) Immobilization of anions via metal sites in the MOF. Leveraging these advantages, the chelating MOF-modified NCM cathode demonstrates reduced charge transfer resistance, both in their pristine and cycled states. In addition, they exhibit significantly improved lithium-ion diffusion coefficients after 100 cycles. These findings underscore the potential of MOFs with chelating agents as promising additive materials for enhancing the performance of LIBs.

Reactive oxygen species-responsive clicked assembly of gold nanoparticles to enhance photothermal therapy.

To enhance the efficacy of photothermal therapy (PTT) at tumor sites, we designed a reactive oxygen species (ROS)-responsive gold nanoparticle (AuNP)-based nanosystem in which azide-decorated AuNPs (N3@AuNPs) and diselenide-coated alkyne-decorated AuNPs (Se/Ak@AuNPs) were separately prepared for selective clicking into nanoclusters when exposed to ROS. Se/Ak@AuNPs were dual-functionalized with alkyne moieties and diselenide linkers embedded in a long chain of polyethylene glycol (PEG) to enable the alkyne moieties of Se/Ak@AuNPs to be inaccessible to the azide moieties of N3@AuNPs owing to steric hindrance. At tumor sites where the ROS level is elevated due to the increased metabolic activity, cellular receptor signaling, mitochondrial dysfunction, and oncogene activity, the diselenide linkers were cleaved, leading to the liberation of the long PEG chains tethered to AuNPs, and the alkyne moieties could be recognized by the surrounding azide moieties to generate a click reaction. The clicked AuNPs formed clustered nanoparticles with increased size. Upon 808 nm laser irradiation, these large clusters of AuNPs significantly enhanced the photothermal conversion efficiency compared with that of isolated AuNPs. In vitro studies revealed that the AuNP clusters exhibited a noticeably higher apoptosis rate than AuNPs. Therefore, ROS-responsive clicked AuNP clusters can be a potential tool for PTT enhancement in cancer treatment.

Highly selective and quantitative in situ monitoring of cell surface proteins by SERS immunoassay system.

Due to their pivotal roles in many biological functions, cell surface proteins (CSPs) are often used for cancer prognosis, as evidenced by a number of studies that have reported significant changes in the expression levels of specific surface proteins depending on the stage of tumorigenesis and selection/variety of reprogrammed cells during cell fate conversion. Current CSP detection strategies suffer from poor selectivity and lack the ability for in situ analysis but maintain the spatial information between cells. Here, we have fabricated nanoprobes for surface-enhanced Raman scattering (SERS) immunoassays by conjugating a specific antibody onto silica-coated gold nanoparticles incorporating an individual Raman reporter (Au-tag@SiO2-Ab NPs) for highly sensitive and selective in situ detection in different types of cells. When multiple HEK293 cell lines stably expressing different levels of the CSP, ACE2, were investigated by the SERS immunoassay, we demonstrated that the level of ACE2 expression in each cell line could be statistically distinguished from that in the other cell lines, indicating the quantitative feature of this biosensing system. When detecting living cells without cell lysis or fixation, as well as fixed cells, the levels of the epithelial CSPs, EpCAM (epithelial cell adhesion molecule) and E-cadherin, were successfully determined using our Au-tag@SiO2-Ab NPs and SERS immunoassay system in a highly selective and quantitative manner without significant cytotoxicity. Hence, our work provides technical insight into the development of a biosensing platform for a variety of biomedical applications, such as cancer metastasis prognosis and the in situ monitoring of stem cell reprogramming and differentiation.

Dual irradiation-triggered anticancer therapeutics composed of polydopamine-coated gold nanoparticles.

The therapeutic efficacy of nanoparticles depends on their ability to release encapsulated photosensitizers. Here, surface-engineered metallic gold nanoparticles (AuNP) were irradiated with dual near-infrared (NIR) light to enhance the release of photosensitizer. Dopamine hydrochloride was surface-polymerized to polydopamine (PDA) layers on AuNP, and chlorin-e6 (Ce6) was chemically tethered to primary amines of PDA. The resulting Ce6-conjugated AuNP were characterized by Raman and X-ray photoelectron spectroscopy and visualized by electron microscopy and light scattering. The generation of reactive oxygen species was increased following dual NIR irradiation at 650 nm and 808 nm, which was attributed to the increased liberation of Ce6. In vitro, dual NIR irradiation significantly enhanced the anticancer effect of Ce6-incorporating AuNP by increasing the population of apoptotic cells. In vivo, tumor xenografted animals exhibited much better tumor suppression when subjected to dual NIR irradiation. Thus, we propose the use of Ce6-incorporating AuNP coupled to dual NIR irradiation for future anticancer treatment of solid tumors.

Fluorescence-Shadowing Nanoparticle Clusters for Real-Time Monitoring of Tumor Progression.

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol) [PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.

Atom transfer radical-polymerized cationic shells on gold nanoparticles for near infrared-triggered photodynamic therapy of tumor-bearing animals.

Gold nanoparticles (AuNPs) were surface-engineered with a cationic corona to enhance the incorporation of photosensitizers for photodynamic therapy (PDT). The cationic corona composed of poly(2-(dimethylamino)ethyl methacrylate) was atom transfer radical-polymerized on the surface of the AuNPs. The cationic corona of the engineered surface was characterized by dynamic light scattering, electron microscopy, Raman spectroscopy, and mass spectroscopy. Chlorin-e6 (Ce6) incorporated onto the surface-engineered AuNPs exhibited higher cell incorporation efficiency than bare AuNPs. Ce6-incorporated AuNPs were confirmed to release singlet oxygen upon NIR irradiation. Compared to Ce6, Ce6-incorporated AuNPs exhibited higher cellular uptake and cytotoxicity against cancer cells in an irradiation time-dependent manner. Near-infrared-irradiated animals administered Ce6-incorporated AuNPs exhibited higher levels of tumor suppression without noticeable body weight loss. This result was attributed to the higher localization of Ce6 at the tumor sites to induce cancer cell apoptosis. Thus, we envision that engineered AuNPs with cationic corona can be tailored to effectively deliver photosensitizers to tumor sites for photodynamic therapy.

Understanding Thermal Behavior of Poly(ethylene glycol)-block-poly(N-isopropylacrylamide) Hydrogel Using Two-Dimensional Correlation Infrared Spectroscopy.

In this study, one of the thermoresponsive polymers, block copolymer consisting of poly(ethylene glycol) and poly(N-isopropylacylamide), was investigated using Fourier transform infrared (FT-IR) spectroscopy, principal component analysis (PCA), and two-dimensional correlation spectroscopy (2D-COS). The apparent trend of the spectral changes in the temperature-dependent FT-IR spectra of poly(ethylene glycol)-block-poly(N-isopropylacylamide) (PEG-b-PNiPAAm) hydrogel during the heating process looks similar to that during the cooling process. The results of the PCA and 2D-COS, however, clearly indicate an irreversible phase transition mechanism of PEG-b-PNiPAAm hydrogel during the heating and cooling processes. It has been also shown that PEG affects the phase transition mechanism of PEG-b-PNiPAAm hydrogel, especially during the heating process. Consequently, we can successfully determine the phase transition temperature and the mechanism of PEG-b-PNiPAAm hydrogel during the heating and cooling processes using PCA and 2D-COS, respectively.

S100A8/A9 mediate the reprograming of normal mammary epithelial cells induced by dynamic cell-cell interactions with adjacent breast cancer cells.

To understand the potential effects of cancer cells on surrounding normal mammary epithelial cells, we performed direct co-culture of non-tumorigenic mammary epithelial MCF10A cells and various breast cancer cells. Firstly, we observed dynamic cell-cell interactions between the MCF10A cells and breast cancer cells including lamellipodia or nanotube-like contacts and transfer of extracellular vesicles. Co-cultured MCF10A cells exhibited features of epithelial-mesenchymal transition, and showed increased capacity of cell proliferation, migration, colony formation, and 3-dimensional sphere formation. Direct co-culture showed most distinct phenotype changes in MCF10A cells followed by conditioned media treatment and indirect co-culture. Transcriptome analysis and phosphor-protein array suggested that several cancer-related pathways are significantly dysregulated in MCF10A cells after the direct co-culture with breast cancer cells. S100A8 and S100A9 showed distinct up-regulation in the co-cultured MCF10A cells and their microenvironmental upregulation was also observed in the orthotropic xenograft of syngeneic mouse mammary tumors. When S100A8/A9 overexpression was induced in MCF10A cells, the cells showed phenotypic features of directly co-cultured MCF10A cells in terms of in vitro cell behaviors and signaling activities suggesting a S100A8/A9-mediated transition program in non-tumorigenic epithelial cells. This study suggests the possibility of dynamic cell-cell interactions between non-tumorigenic mammary epithelial cells and breast cancer cells that could lead to a substantial transition in molecular and functional characteristics of mammary epithelial cells.

Studies on Chemical IR Images of Poly(hydroxybutyrate⁻co⁻hydroxyhexanoate)/Poly(ethylene glycol) Blends and Two-Dimensional Correlation Spectroscopy.

Biodegradable poly-[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoates] (PHBHx) have been widely studied for their applications in potentially replacing petroleum-based thermoplastics. In this study, the effect of the high molecular weight (Mn = 3400) poly(ethylene glycol) (PEG) blended in the films of PHBHx with different ratios of PEG was investigated using chemical FTIR imaging. Chemical IR images and FTIR spectra measured with increasing temperature revealed that PEG plays an important role in changing the kinetics of PHBHx crystallization. In addition, two-dimensional correlation spectra clearly showed that thermal properties of PHBHx/PEG blend film changed when the blending ratio of PHBHx/PEG were 60/40 and 50/50. Consequently, PEG leads to changes in the thermal behavior of PHBHx copolymers.

Highly sensitive determination of iron (III) ion based on phenanthroline probe: Surface-enhanced Raman spectroscopy methods.

In this paper, we introduced Raman spectroscopy techniques that were based on the traditional Fe3+ determination method with phenanthroline as a probe. Interestingly, surface-enhanced Raman spectroscopy (SERS)-based approach exhibited excellent sensitivities to phenanthroline. Different detection mechanisms were observed for the RR and SERS techniques, in which the RR intensity increased with increasing Fe3+ concentration due to the observation of the RR effect of the phenanthroline-Fe2+ complex, whereas the SERS intensity increased with decreasing Fe3+ concentration due to the observation of the SERS effect of the uncomplexed phenanthroline. More importantly, the determination sensitivity was substantially improved in the presence of a SERS-active substrate, giving a detection limit as low as 0.001µg/mL, which is 20 times lower than the limit of the UV-vis and RR methods. Furthermore, the proposed SERS method was free from other ions interference and can be used quality and sensitivity for the determination of the city tap water.

Salt Triggers the Simple Coacervation of an Underwater Adhesive When Cations Meet Aromatic π Electrons in Seawater.

Adhesive systems in many marine organisms are postulated to form complex coacervates (liquid-liquid phase separation) through a process involving oppositely charged polyelectrolytes. Despite this ubiquitous speculation, most well-characterized mussel adhesive proteins are cationic and polyphenolic, and the pursuit of the negatively charged proteins required for bulk complex coacervation formation internally remains elusive. In this study, we provide a clue for unraveling this paradox by showing the bulky fluid/fluid separation of a single cationic recombinant mussel foot protein, rmfp-1, with no additional anionic proteins or artificial molecules, that is triggered by a strong cation-π interaction in natural seawater conditions. With the similar condition of salt concentration at seawater level (>0.7 M), the electrostatic repulsion between positively charged residues of mfp-1 is screened significantly, whereas the strong cation-π interaction remains unaffected, which leads to the macroscopic phase separation (i.e., bulky coacervate formation). The single polyelectrolyte coacervate shows interesting mechanical properties including low friction, which facilitates the secretion process of the mussel. Our findings reveal that the cation-π interaction modulated by salt is a key mechanism in the mussel adhesion process, providing new insights into the basic understanding of wet adhesion, self-assembly processes, and biological phenomena that are mediated by strong short-range attractive forces in water.

Quantitative Determination of Iron Ions Based on a Resonance Raman (RR) Probe-Phenanthroline.

In this paper, we demonstrate a new promising resonance Raman (RR)-based method for the determination of Fe3+ concentrations in aqueous solutions. Iron ions were quantified at a low concentration range by employing hydroxylamine hydrochloride as the reductant, and phenanthroline as the complexing agent, thereby reducing Fe3+ to Fe2+. The addition of Fe3+ to the detection reagent resulted in a rapid color change from colorless to orange-red, together with an obvious new RR band appearing at 1459 cm-1. Herein, the RR intensity of the phenanthroline-Fe2+ complex strengthened with increasing Fe3+ concentration, which was identified from the variation of the Raman spectra. Therefore, we successfully detected Fe3+ at lower concentrations using the proposed method, illustrating its great potential for the detection of Fe3+ with abundant RR fingerprint information. More importantly, the proposed method exhibited a wide liner range from 0.05 to 10 µg/mL.

Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1-Regulating Anti-inflammatory Agents.

Sepsis is one of the major causes of death worldwide when associated with multiple organ failure. However, there is a critical lack of adequate sepsis therapies because of its diverse patterns of pathogenesis. The pro-inflammatory cytokine cascade mediates sepsis pathogenesis, and high mobility group box proteins (HMGBs) play an important role as late-stage cytokines. We previously reported the small-molecule modulator, inflachromene (1d), which inhibits the release of HMGBs and, thereby, reduces the production of pro-inflammatory cytokines. In this context, we intraperitoneally administered 1d to a cecal ligation and puncture (CLP)-induced mouse model of sepsis and confirmed that it successfully ameliorated sepsis pathogenesis. On the basis of a structure-activity relationship study, we discovered new candidate compounds, 2j and 2l, with improved therapeutic efficacy in vivo. Therefore, our study clearly demonstrates that the regulation of HMGB1 release using small molecules is a promising strategy for the treatment of sepsis.

IL-1ß induces IL-6 production and increases invasiveness and estrogen-independent growth in a TG2-dependent manner in human breast cancer cells.

BACKGROUND: We previously reported that IL-6 and transglutaminase 2 (TG2) were expressed in more aggressive basal-like breast cancer cells, and TG2 and IL-6 expression gave these cells stem-cell-like phenotypes, increased invasive ability, and increased metastatic potential. In the present study, the underlying mechanism by which IL-6 production is induced in luminal-type breast cancer cells was evaluated, and TG2 overexpression, IL-1ß stimulation, and IL-6 expression were found to give cancerous cells a hormone-independent phenotype. METHODS: Luminal-type breast cancer cells (MCF7 cells) were stably transfected with TG2. To evaluate the requirement for IL-6 neogenesis, MCF7 cells were stimulated with various cytokines. To evaluate tumorigenesis, cancer cells were grown in a three-dimensional culture system and grafted into the mammary fat pads of NOD/scid/IL-2Rγ(-/-) mice. RESULTS: IL-1ß induced IL-6 production in TG2-expressing MCF7 cells through an NF-kB-, PI3K-, and JNK-dependent mechanism. IL-1ß increased stem-cell-like phenotypes, invasiveness, survival in a three-dimensional culture model, and estrogen-independent tumor growth of TG2-expressing MCF7 cells, which was attenuated by either anti-IL-6 or anti-IL-1ß antibody treatment. CONCLUSION: Within the inflammatory tumor microenvironment, IL-1ß increases luminal-type breast cancer cell aggressiveness by stimulating IL-6 production through a TG2-dependent mechanism.

High-yield clicking and dissociation of doxorubicin nanoclusters exhibiting differential cellular uptakes and imaging.

Gold nanoparticles (AuNPs) and quantum dots (Qdots) were clicked into doxorubicin nanoclusters that showed enzyme-dependent dissociation behaviors for differential cellular uptakes and imaging. The AuNPs were co-functionalized with doxorubicin (DOX) and azide-terminated polymer (DOX/azide@AuNP), while an enzyme-cleavable peptide and alkyne-terminated polymer were sequentially conjugated on Qdot surface (Alkyne-MMP@Qdot). Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, and fluorescence imaging detected the azide and alkyne groups on DOX/azide@AuNP and Alkyne-MMP@Qdot, respectively, and the click-reactivity was also confirmed. In the presence of the catalyst, two nanoparticles were clicked to doxorubicin nanoclusters, which increased the volume of the particles ca. 343-fold within 30min. Upon matrix metalloproteinase-2 (MMP-2) digestion, the nanoclusters were clearly dissociated into smaller particles, and the fluorescence of the quenched Qdot was also recovered, which suggests that the nanoclusters respond to MMP-2 concentrations and can thus be employed for cancer imaging. Confocal microscopy and an elemental analysis of the cancer cells revealed that the cellular uptakes of doxorubicin nanoclusters significantly increased at higher MMP-2 concentrations, and doxorubicin could also be cleaved for anti-cancer effects. In vivo and in vitro cytotoxicity assay accordingly showed that the cytotoxicity of doxorubicin nanoclusters against cancer cells increased in MMP-2-rich environments such as tumor site. Thus, these nanoclusters containing DOX/azide@AuNP and Alkyne-MMP@Qdot are expected to be multifunctional carriers for targeted anti-cancer treatments and imaging.

Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis.

Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells.

BACKGROUND: Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. METHODS: Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells. RESULTS: Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 µM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 µM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. CONCLUSIONS: These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.