Injectable hydrogel platform with biodegradable Dawson-type polyoxometalate and R848 for combinational photothermal-immunotherapy of cancer.

Photothermal therapy (PTT) is a powerful strategy for cancer treatment with minimal invasiveness but still limited by lack of long-term efficacy against tumor recurrence and toxicity concerns about the slow biodegradability of the PTT agents. Herein, an injectable hydrogel platform (R848/POM@GG) of gellan gum co-loaded with Dawson-type {P2Mo18} polyoxometalate (POM) and Toll-like receptors agonist resiquimod (R848) is developed for combinational photothermal-immunotherapy of cancer. The POM-based gellan gum hydrogel (POM@GG) exhibits high photothermal conversion efficiency (63.1%) at a safe power density of 0.3 W cm-2 and good photostability during five cycles. By further incorporation of R848, the obtained R848/POM@GG exerts synergetic photothermal-immunotherapy on solid tumors, giving a high tumor inhibition rate of 99.3% and negligible lung metastases in the breast cancer mice models. A strong antitumor immune system with significantly elevated TNF-α, IL-2, and IL-6 levels is activated by R848. Additionally, the POM clusters gradually degrade to nontoxic molybdate in the physiological environment. Overall, the injectable hydrogel platform of R848/POM@GG has great translational potential for localized antitumor treatments.

Microwave-Assisted Synthesis of Tris-Anderson Polyoxometalates for Facile CO2 Cycloaddition.

Four new tris-Anderson polyoxometalates (POMs), (NH4)4[ZnMo6O18(C4H8NO3)(OH)3]·4H2O (1), (NH4)4[CuMo6O18(C4H8NO3)(OH)3]·4H2O (2), (TBA)3(NH4)[ZnMo6O17(C5H9O3)2(OH)]·10H2O (3) (TBA = n-C16H36N), and (NH4)4[CuMo6O18(C5H9O3)2]·16H2O (4), were synthesized by a microwave-assisted method. Single-crystal X-ray diffraction revealed that 1 and 2 contained a tris (trihydroxyl organic compounds) ligand grafted on one side, while two tris ligands were grafted on two sides to form χ/δ and δ/δ isomers in 3 and 4, respectively. 1H and 13C NMR spectra of the χ/δ isomer 3 were obtained for the first time, with six methylenes showing six peaks in the 1H NMR spectrum and only four peaks in the 13C NMR spectrum. Mass spectrometry monitoring revealed that during the microwave-assistant process the tris ligand can graft onto POMs to form 1, while tris directly coordinates with metallic heteroatoms to form isopolymolybdates during the conventional reflux synthesis process. In addition, 1-4 can catalyze CO2 with epoxides into cyclic carbonates with high selectivity and yields at an atmospheric pressure of CO2, which is lower than the pressure of CO2 in other catalysis using POMs as catalysts. Furthermore, 1-4 showed good catalytic stability and cycling properties. Mechanism studies substantiated POMs cocatalyzed with Br- to improve the catalytic yields.

Lipopolysaccharide potentiates dopaminergic neuronal dysfunction in α-synuclein transgenic mice / 药学学报

Parkinson's disease (PD) is the most prevalent neurodegenerative disorder, with several risk factors contributing to the onset, such as aging, genetics, oxidative stress and neuroinflammation. There are several PD animals that mimics different risk factor. α-Synuclein mutation mice and systemic lipopolysaccharide (LPS) injection mice are two kinds of most common animal models that replicate genetic mutation and neuroinflammation, respectively. However, in these two animal models, the pathogenesis occurred after a long period of stimulation. In the present study, four-month-old α-synucleintransgenic mice (A53T) were intraperitoneally injected with LPS once a week for continuous 8 weeks to simulate the inflammatory response. The behavioral results showed that the time of mice staying on the rod and the performance score were markedly decreased, indicating motor dysfunction. Dopaminergic neuronal function also decreased. It was noted that the movement dysfunction and pathological changes were aggravated in LPS plus α-synuclein challenged mice compared with LPS or α-synuclein stimulated alone, suggesting that the double attack had synergistic effects. Mechanistic study demonstrated that LPS and α-synuclein combined challenge led to obvious neuroinflammatory response and apoptosis, which might contribute to motor and dopaminergic neuronal dysfunction. In addition, differential proteomic study showed that the expression of CD99L2 and COX7RP significantly increased in the midbrain of LPS plus α-synuclein challenged mice, which were closely related to inflammation and apoptosis, and might be involved in the pathogenesis of PD. In conclusion, the present study demonstrated that LPS could potentiate dopaminergic neuronal function in α-synuclein transgenic mice, which might be an ideal method to develop PD animal model.

Diversity and distribution of the threatened medicinal vascular plants in Lancang / 中国中药杂志

The rich diversity in medicinal plants provides an important material basic for the development of Traditional Chinese medicine in China. It is important to explore the present situation of medicinal plants within special regions in order to provide scientific instructions for their sustainable protection and exploitation and utilization. In this study, we carried out the field survey according to the guideline of national survey of Chinese material medica resources and the guideline of plant species diversity survey and estimation at county level with the line transect method. With the field surveyed data, we explored the diversity and distribution of the threatened medicinal vascular plants in Lancang. We found that there were 33 species of the threatened medicinal vascular plants in this county. These species were from 23 genera and 17 families, and were composed of one critical endangered, 10 endangered and 22 vulnerable species. They were widely distributed across the whole county and were most concentrated in the town of Nuozhadu, Fazhanhe, Nuofu and Zhutang, which were located in the southeastern, southwestern and western of Lancang, respectively. We also found that the plant species richness followed a unimodal pattern along elevation. In addition, we found that the areas of Nuozhadu Nature Reserve in Lancang only covered six threatened medicinal vascular plants, while most of the regions with high species richness were not well protected. Therefore, we proposed to make more efforts to improve the protection measurements in order to better protect and utilize the medicinal plants in Lancang.

Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride / 药学学报

This study is to compare the pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone (Mit-lipo) and free mitoxantrone (Mit-free). The antineoplastic effect of Mit-lipo was evaluated on PC-3 human xenograft tumor model after repeated intravenous injection at dose levels of 1, 2 and 4 mg x kg(-1). The pharmacokinetic study of Mit-lipo and Mit-free was performed on dogs following a single intravenous injection. The tissue distribution of Mit-lipo and Mit-free was observed on S-180 bearing mice after a single intravenous injection. (1) Pharmacodynamics: Mit-lipo dose-dependently inhibited PC-3 tumor growth at a dose ranging from 1 to 4 mg x kg(-1). The antitumor effect studies showed that Mit-lipo significantly improved the therapeutic effect in comparison with free drug. (2) Pharmacokinetics: in comparison with Mit-free, the AUC and t(1/2) values of Mit-lipo at the same dose level were higher than those of Mit-free in Beagle dogs. The results showed that Mit-lipo had long circulation characteristics. (3) Tissue distribution in S-180 bearing mice: compared to Mit-free, Mit-lipo preferentially accumulated into tumor zones instead of normal tissues. Tumor AUC in Mit-lipo treated animals was 8.7 fold higher than that in mice treated with the same dose of Mit-free. The Cmax values of Mit-lipo in heart, kidney, lung, spleen and intestinal tissue in Mit-lipo were 30.2%, 161.6%, 20.2%, 27.9% and 78.3% lower than those of Mit-free, respectively. The pharmacokinetics and tissue distribution of Mit-lipo changed obviously, thus increasing therapeutic effect and improving drug therapeutic index.

Determination of adefovir in monkey plasma by liquid chromatography-tandem mass spectrometry / 药学学报

<p><b>AIM</b>To develop a sensitive and specific liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the determination of adefovir in monkey plasma.</p><p><b>METHODS</b>Adefovir and internal standard 9-(3-phosphonylmethoxypropyl) adenine were isolated from plasma by protein precipitation with methanol, then chromatographed by using a Diamonsil C18 column. The mobile phase consisted of methanol-water-formic acid (20:80:1). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Selected reaction monitoring (SRM) mode with the transitions of m/z 274-->m/z 162 and m/z 288-->m/z 176 were used to quantify adefovir and the internal standard, respectively.</p><p><b>RESULTS</b>The linear calibration curve was obtained in the concentration range of 0.02-4.00 mg.L-1. The lower limit of quantitation was 20 micrograms.L-1. The inter- and intra-day precision (RSD) was less than 5.8%, and the accuracy (relative error) was within +/- 4.5%. The method was successfully used in a pharmacokinetic study of adefovir dipivoxil in monkeys.</p><p><b>CONCLUSION</b>The method is proved to be suitable for pre-clinical investigation of adefovir dipivoxil pharmacokinetics, which offers advantages of specificity and simple sample preparation compared with the previously reported methods.</p>

Determination of wogonin in rat plasma by liquid chromatography-tandem mass spectrometry / 药学学报

<p><b>AIM</b>To develop a sensitive and rapid LC/MS/MS method for the determination of wogonin, an active flavonoid shown to have an inhibitory effect on the proliferation of a carcinoma cell line, in rat plasma after an oral administration.</p><p><b>METHODS</b>Wogonin and daidzein (internal standard) were extracted from plasma directly with n-hexane-diethyl ether (1:4). After liquid-liquid extraction, the analytes of interest were separated on a Diamonsil C18 column. The mobile phase was acetonitrile-water-formic acid (80:20:1) with a flow rate of 0.8 mL.min-1. A Finnigan TSQ (triple stage quadruple) tandem mass spectrometer equipped with an atmospheric pressure chemical ionization (APCI) source was used as detector and was operated in positive ion mode. Selected reaction monitoring (SRM) was used and transitions selected for quantitation were: m/z 284.8-->269.5 for wogonin and m/z 254.7-->198.5 for daidzein. The mass spectrometric conditions were as follows: The temperatures of the vaporizer and heated capillary were 450 degrees C and 250 degrees C, respectively. The corona discharge current was 4.00 microA. Nitrogen was used as the sheath and auxiliary gas, whose settings were 0.6 MPa and 3 mL.min-1, respectively. Argon was used as the collision gas at a pressure of 1.4 Pa. The collision energy of 35 V was chosen for both wogonin and daidzein.</p><p><b>RESULTS</b>The calibration curve was linear over the concentration range of 0.25 to 20.0 ng.mL-1. The limit of quantitation was 0.25 ng.mL-1. Within-day and between-day precision expressed by relative standard deviation (RSD) was 2.2% to 13.1% and 5.9% to 7.3%, respectively, and the accuracy expressed by RE was -0.3% to 1.3%.</p><p><b>CONCLUSION</b>This method proved to be specific, accurate and sensitive enough to be applied to the pharmacokinetic studies of wogonin in rats after a single dose of 5 mg.kg-1 by oral administration.</p>