Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma

Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75–110 nm with size dispersion (PDI) within the range of 0.19–0.50 and zeta-potential approximately –10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability—their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.     

Lanostane Triterpenoids and Ergostane Steroids from Ganoderma luteomarginatum and Their Cytotoxicity

Macrofungus Ganoderma luteomarginatum is one of the main species of Ganoderma fungi distributed in Hainan province of China, the fruiting bodies of which have been widely used in folk as a healthy food to prevent tumors. To explore the potential cytotoxic constituents from G. luteomarginatum, the phytochemical investigation on the ethyl acetate soluble fraction of 95% ethanolic extract from the fruiting bodies of this fungus led to the isolation of twenty-six lanostane triterpenoids (1–26), including three undescribed ones (1–3), together with eight ergostane steroids (27–34). The structures of three new lanostane triterpenoids were elucidated as lanosta-7,9(11)-dien-3β-acetyloxy-24,25-diol (1), lanosta-7,9(11)-dien-3-oxo-24,26-diol-25-methoxy (2), and lanosta-8,20(22)-dien-3,11,23-trioxo-7β,15β-diol-26-oic acid methyl ester (3) by the analysis of 1D, 2D NMR, and HRESIMS spectroscopic data. All isolates were assayed for their cytotoxic activities using three human cancer cell lines (K562, BEL-7402, and SGC-7901) and seven lanostane triterpenoids (1, 2, 7, 13, 18, 22, and 24), and one ergostane steroid (34) showed definite cytotoxicity with IC₅₀ values that ranged from 6.64 to 47.63 μg/mL. Among these cytotoxic lanostane triterpenoids, compounds 2 and 13 showed general cytotoxicity against three human cancer cell lines, while compounds 1 and 18 exhibited significant selective cytotoxicity against K562 cells with IC₅₀ values of 8.59 and 8.82 μg/mL, respectively. Furthermore, the preliminary structure–cytotoxicity relationships was proposed.     

Alkaloid Derivative (Z)-3β-Ethylamino-Pregn-17(20)-en Inhibits Triple-Negative Breast Cancer Metastasis and Angiogenesis by Targeting HSP90α

Metastasis is an important cause of cancer-related death. Previous studies in our laboratory found that pregnane alkaloids from Pachysandra terminalis had antimetastatic activity against breast cancer cells. In the current study, we demonstrated that treatment with one of the alkaloid derivatives, (Z)-3β-ethylamino-pregn-17(20)-en (1), led to the downregulation of the HIF-1α/VEGF/VEGFR2 pathway, suppressed the phosphorylation of downstream molecules Akt, mTOR, FAK, and inhibited breast cancer metastasis and angiogenesis both in vitro and in vivo. Furthermore, the antimetastasis and antiangiogenesis effects of 1 treatment (40 mg/kg) were more effective than that of Sorafenib (50 mg/kg). Surface plasmon resonance (SPR) analysis was performed and the result suggested that HSP90α was a direct target of 1. Taken together, our results suggested that compound 1 might represent a candidate antitumor agent for metastatic breast cancer.     

Oxidative Desulfurization Activity of NIT Nitroxide Radical Modified Metallophthalocyanine

In the present study, metallophthalocyanines were modified with NIT nitroxide radicals through chemical bonds to prepare a series of metallophthalocyanines–NIT catalysts (MPcTcCl₈-NIT, M=Mn²⁺, Fe²⁺, Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺) applied for oxidative desulfurization of thiophene (T) in model fuel. The MPcTcCl₈-NIT catalysts were characterized by FTIR, UV-Vis, ESR, and XPS spectra. The oxidative desulfurization activity of MPcTcCl₈-NIT catalysts was studied in a biomimetic catalytic system using molecular O₂ as the oxidant. The MPcTcCl₈-NIT catalysts exhibited high catalytic activities for the oxidation of thiophene in model fuel. The desulfurization rate of ZnPcTcCl₈-NIT for thiophene reached to 99.61%, which was 20.53% higher than that of pure ZnPcTcCl₈ (79.08%) under room temperature and natural light. The results demonstrated that MPcTcCl₈-NIT catalysts could achieve more effective desulfurization rate under milder conditions than that of the metallophthalocyanines. The NIT nitroxide radicals also could improve the catalytic activity of metallophthalocyanine based on the synergistic oxidation effect. The stability experiments for ZnPcTcCl₈-NIT showed that the catalyst still had a high desulfurization rate of 92.37% after five times recycling. All these findings indicate that the application of MPcTcCl₈-NIT catalysts provides a potential new way for the desulfurization performance of thiophene in fuel.     

Analyze the Effect of Steaming on the Chemical Constituents,Defecation and Liver Injury of Polygonum Multiflorum Radix (Heshouwu) by Multiple Analysis Techniques Combined with Multivariate Statistics

Steaming is a characteristic pharmaceutical skill in Traditional Chinese Medicine (TCM). Polygonum multiflorum radix (PM) and its steamed products have been used in Asia for centuries. Raw Polygonum multiflorum radix (RPM) is commonly used to promote defecation but can exert toxicity, especially in liver injury. However, RPM can be made converted into Polygoni multiflori radix praeparata (PMP) by steaming; this is considered a good method to reduce defecation and liver injury caused by PM in Asia. The chemical constituents of TCM are the key to its action. We systematically analyzed the effect of steaming on PM constituents, defecation, and liver injury. We identified 13 main constituents from PM and PMP; the results showed that after being steamed, two constituents (TSG, catechin) had decreased, six constituents (such as procyanidin B1 or B2) had disappeared, four constituents (such as emodin, physcion) had increased, emodin-8-O-β-D-glucoside remained unchanged in PMP. Pharmacological experiments showed that PM could promote defecation; however, there were no obvious effects in response to PMP. Only a high dose of PM for 14 days caused some degree of liver injury, although this injury disappeared after 14 days of drug withdrawal. Network pharmacology and molecular docking studies showed that TSG, emodin and physcion were the most effective in promoting defecation and causing liver injury. Collectively, our findings show that steaming can reduce the effect of PM on promoting defecation and reducing liver injury. TSG may be one of the important constituents in PM that can promote defecation and cause liver injury.     

Photophysical and Primary Self-Referencing Thermometric Properties of Europium Hydrogen-Bonded Triazine Frameworks

Lanthanide hydrogen-bonded organic frameworks (LnHOFs) are recently emerging as a novel versatile class of multicomponent luminescent materials with promising potential applications in optics and photonics. Trivalent europium (Eu³⁺) incorporated polymeric hydrogen-bonded triazine frameworks (PHTF:Eu) have been successfully obtained via a facile and low-cost thermal pyrolysis route. The PHTF:Eu material shows a porous frame structure principally composed of isocyanuric acid and ammelide as a minor constituent. Intense red luminescence with high colour-purity from Eu³⁺ is obtained by exciting over a broad absorption band peaked at 300 nm either at room or low temperature. The triazine-based host works as excellent optical antenna towards Eu³⁺, yielding ~42% sensitization efficiency (η_sens) and an intrinsic quantum yield of Eu³⁺ emission (Φ_Eu) as high as ~46%. Temperature-dependent emission studies show that PHTF:Eu displays relatively high optical stability at elevated temperatures in comparison to traditional inorganic phosphors. The retrieved activation energy of 89 meV indicates that thermal quenching mechanisms are attributed to the intrinsic energy level structure of the metal-triazine assembly, possibly via a thermally activated back transfer to ligand triplet or CT states. Finally, by using an innovative approach based on excitation spectra, we demonstrate that PHTF:Eu can work as a universal primary self-referencing thermometer based on a single-emitting center with excellent relative sensitivity in the cryogenic temperature range.     

Cold Sintering of Li6.4La3Zr1.4Ta0.6O12/PEO Composite Solid Electrolytes

Ceramic/polymer composite solid electrolytes integrate the high ionic conductivity of in ceramics and the flexibility of organic polymers. In practice, ceramic/polymer composite solid electrolytes are generally made into thin films rather than sintered into bulk due to processing temperature limitations. In this work, Li_6.4La₃Zr_1.4Ta_0.6O₁₂ (LLZTO)/polyethylene-oxide (PEO) electrolyte containing bis(trifluoromethanesulfonyl)imide (LiTFSI) as the lithium salt was successfully fabricated into bulk pellets via the cold sintering process (CSP). Using CSP, above 80% dense composite electrolyte pellets were obtained, and a high Li-ion conductivity of 2.4 × 10⁻⁴ S cm^–1 was achieved at room temperature. This work focuses on the conductivity contributions and microstructural development within the CSP process of composite solid electrolytes. Cold sintering provides an approach for bridging the gap in processing temperatures of ceramics and polymers, thereby enabling high-performance composites for electrochemical systems.     

Nano-Theranostics Constructed from Terpyridine-Modified Pillar [5]arene-Based Supramolecular Amphiphile and Its Application in Both Cell Imaging and Cancer Therapy

Theranostics play an important role in cancer treatment due to its realized real-time tracking of therapeutic efficacy in situ. In this work, we have designed and synthesized a terpyridine-modified pillar [5]arenes (TP5). By the coordination of terpyridine and Zn²⁺, the complex TP5/Zn was obtained. Then, supramolecular amphiphile can be constructed by using host–guest complexation between a polyethylene glycol contained guest (PM) and TP5/Zn. Combining the fluorescence properties from the terpyridine group and the amphiphilicity from the system, the obtained TP5/Zn/PM can further be self-assembled into fluorescent particles with diameters of about 150 nm in water. The obtained particles can effectively load anti-cancer drugs and realize living cell imaging and a precise release of the drugs.     

Fabrication of Orange Fluorescent Boron-Doped Graphene Quantum Dots for Al3+ Ion Detection

Aluminum is a kind of metal that we often encounter. It can also be absorbed by the human body invisibly and will affect our bodies to a certain extent, e.g., by causing symptoms associated with Alzheimer’s disease. Therefore, the detection of aluminum is particularly important. The methods to detect metal ions include precipitation methods and electrochemical methods, which are cumbersome and costly. Fluorescence detection is a fast and sensitive method with a low cost and non-toxicity. Traditional fluorescent nanomaterials have a high cost, high toxicity, and cause harm to the human body. Graphene quantum dots are a new type of fluorescent nanomaterials with a low cost and non-toxicity that can compensate for the defects of traditional fluorescent nanomaterials. In this paper, c-GQDs and o-GQDs with good performance were prepared by a bottom-up hydrothermal method using o-phenylenediamine as a precursor and citric acid or boric acid as modulators. They have very good optical properties: o-GQDs exhibit orange fluorescence under UV irradiation, while c-GQDs exhibits cyan fluorescence. Then, different metal ions were used for ion detection, and it was found that Al³⁺ had a good quenching effect on the fluorescence of the o-GQDs. The reason for this phenomenon may be related to the strong binding of Al³⁺ ions to the N and O functional groups of the o-GQDs and the rapid chelation kinetics. During the chelation process, the separation of o-GQDs’ photoexcited electron hole pairs leads to their rapid electron transfer to Al³⁺, in turn leading to the occurrence of a fluorescence-quenching phenomenon. In addition, there was a good linear relationship between the concentration of the Al³⁺ ions and the fluorescence intensity, and the correlation coefficient of the linear regression equation was 0.9937. This illustrates the potential for the wide application of GQDs in sensing systems, while also demonstrating that Al³⁺ sensors can be used to detect Al³⁺ ions.