Engineering near-infrared laser-activated gold nanorod vesicles with upper critical solution temperature for photothermal therapy and chemotherapy.

Multimodal synergistic therapy based on nanomedicine drug delivery systems can achieve accurate cancer treatment. The anisotropy of gold nanorods (AuNRs) allows the adjustment of the longitudinal localized surface plasmon resonance absorption to the near-infrared band, which shows potential application in the field of photothermal therapy of cancer. Here, we report a new type of thermal-sensitive gold nanorod drug-loaded vesicles (UGRV-DOX) via the self-assembly of AuNRs modified with the amphiphilic polymer (PEG45-b-PS150) and upper critical solution temperature (UCST) polymer (P(AAm-co-AN)). The hollow structure of the vesicle can increase the drug loading capacity, and the polymers on its surface are intertwined to reduce drug leakage. As-prepared UGRV-DOX vesicles exhibits excellent photothermal conversion efficiency and can achieve light-controlled drug release. In vivo anti-tumor experiments showed that UGRV-DOX could ablate HepG2 transplanted tumors significantly under 808 nm laser irradiation, and the inhibition rate was as high as 99.3 %. These tumor-specific nanovesicles prefigure great potentials for high-precision cancer treatment.

Engineering naphthalimide-cyanine integrated near-infrared dye into ROS-responsive nanohybrids for tumor PDT/PTT/chemotherapy.

Photodynamic (PDT) and photothermal therapies (PTT) are emerging treatments for tumour ablation. Organic dyes such as porphyrin, chlorin, phthalocyanine, boron-dipyrromethene and cyanine are the clinically or preclinically used photosensitizer or photothermal agents. Development of structurally diverse near-infrared dyes with long absorption wavelength is of great significance for PDT and PTT. Herein, we report a novel near-infrared dye ML880 with naphthalimide modified cyanine skeleton. The introduction of naphthalimide moiety results in stronger electron delocalization and larger redshift in emission compared with IR820. Furthermore, ML880 is co-loaded with chemotherapeutic drug into ROS-responsive mesoporous organosilica (RMON) to construct nanomedicine NBD&ML@RMON, which exhibits remarkable tumor inhibition effects through PDT/PTT/chemotherapy in vivo.

Novel Inhibitors of an Insect Pest Chitinase: Design and Optimization of 9-O-Aromatic and Heterocyclic Esters of Berberine.

OfChi-h, a lepidopteran-exclusive glycoside hydrolase family 18 (GH18) chitinase from the agricultural insect pest Ostrinia furnacalis, is a promising molecular target candidate for pest control and management. Berberine (BER), a traditional Chinese medicine, binds to a wide variety of glycosyl hydrolases via an identical mechanism, showing potential as a pesticide lead compound. In this work, we found that BER was a moderate inhibitor of OfChi-h with a Ki of 16.1 µM. To improve its efficacy, a series of BER derivatives featuring an ester bond linked to an aromatic or heterocyclic aromatic ring at the 9-position were designed and evaluated as effective OfChi-h inhibitors. The most potent compound, compound 19e with a nicotinate group, exhibited a Ki of 0.093 µM. Molecular docking analysis suggested that the common binding mode of BER derivatives featured a network of π-π stacking and electrostatic interactions and that the group at the 9-position enhanced the van der Waals and hydrogen bonding interactions. Administration of the BER derivative 19c to 4th-instar O. furnacalis larvae in an artificial diet led to their impaired growth and metamorphosis. This work provides a new starting point for the modification of BER for use in pest control.

Dual-responsive nanohybrid based on degradable silica-coated gold nanorods for triple-combination therapy for breast cancer.

Multi-modal combination therapy has attracted great attention, owing to the unsatisfactory therapeutic efficacy of conventional chemotherapy. Mesoporous silica-coated gold nanorods possess great potential in photothermal therapy and drug delivery. In this work, we fabricate a dual-responsive nanohybrid for combination treatment of the malignant tumor. In this system, gold nanorods are coated with the degradable mesoporous silica, and the chemotherapy drug doxorubicin (DOX) and photosensitizer (IR820) are co-loaded inside the pores of the silica. The encapsulation of hyaluronic acid (HA) endow the nanohybrids with mammary carcinoma targeting ability and better biocompatibility, owning to CD44+ receptor overexpressed in some cancer cells. As-prepared nanohybrids exhibit high responsiveness to a high glutathione (GSH) level and degrade rapidly in the presence of hyaluronidase (HAase) and GSH after endocytosis by 4T1 cells, allowing the efficient release of loaded DOX and IR 820 in tumor sites. Interestingly, near-infrared (NIR) laser not only triggers the generation of reactive oxygen species, but also remarkable photothermal efficacy originating from GNRs. Therefore, upon the irradiation of 808 nm NIR light, the combinatorial photodynamic, photothermal and chemotherapy is achieved, accordingly leading to a highly efficient antitumor outcome in vitro and in vivo. This strategy provides an ideal approach to constructing multimodal cancer therapy system. STATEMENT OF SIGNIFICANCE: • Dual-responsive nanohybrids for combinatorial therapy of breast cancer. • The nanohybrids exhibit both HAase and GSH stimuli-responsive behavior. • The nanohybrids exhibit light-activated PDT/PTT/chemotherapy. • The nanohybrids show good biosafety for potential clinical application.

Removal of mercury from aqueous solution using mesoporous silica nanoparticles modified with polyamide receptor.

Based on the principle of supramolecular recognition and fluorescent chemical sensors, a novel kind of material for the separation of toxic heavy metal ions was designed and synthesized. Mesoporous silica nanoparticles MCM-41 with high surface areas and large ordered pores were used as the supporting matrix. Poly-amide derivative, was grafted to the mesoporous silica nanoparticles for extracting and separating trace Hg(2+) from aqueous solution, with a short adsorption time (t=3min) and a wide range of pH application (pH 3-11). The separation material could also extract trace mercury from Traditional Chinese Medicine, and has no influence on their effective components.

Discrimination and classification of ginsenosides and ginsengs using bis-boronic acid receptors in dynamic multicomponent indicator displacement sensor arrays.

Ginsenosides are complex natural products with a diverse array of biological activities, but their molecular recognition and sensing is challenging. A library of simple bis-boronic acid-based receptors with various spacers was synthesized for the sensing of ginsenosides. The incorporation of two boronic acids allowed the pairing of two indicators, which can simultaneously bind the receptors or two saccharides within the ginsenosides. A cross-reactive sensing array was therefore constructed using the receptors in conjunction with different pairs of indicators. LDA plots created from the colorimetric response of the hosts and indicator pairs reveal excellent classification of the ginsenosides, and the corresponding loading plots reveal the cross-reactivity of the receptors. In addition, several commercial ginseng extracts were unambiguously classified using the same sensing array. The assay reported here should be applicable to the analysis of other large saccharide-based natural products.

7-b, a novel amonafide analogue, cause growth inhibition and apoptosis in Raji cells via a ROS-mediated mitochondrial pathway.

Previous studies have shown that 7-b (6-(dodecylamino)-2-(3-(4-methylpiperazin-1-yl)propyl)-1H-benzo-[de]isoquinoline-1,3(2H)-dione), a novel amonafide-based DNA intercalator, was generated as a new anticancer candidate. However, the effects induced by 7-b and the molecular mechanisms involved remain poorly understood in Burkitt's lymphoma. To shed light on these issues, we have investigated the effects of 7-b on proliferation, cell cycle progression, apoptosis activity and oxidative stress levels of lymphoma Raji cells in vitro. Our results showed that 7-b inhibited the proliferation of Raji cells and induced G1 cell cycle arrest in a dose-dependent manner. Moreover, 7-b treatment triggered programmed cell death, production of reactive oxygen species (ROS) and alteration of the mitochondrial membrane potential (Δψm). Altogether our results showed that 7-b mediated its growth inhibitory effects on Raji cells via the activation of a ROS-mediated mitochondrial pathway and cell cycle checkpoint signaling pathway which subsequently targeted p21.

Recent progress of highly efficient in vivo biological screening for novel agrochemicals in China.

This paper describes the recent progress of in vivo biological screening for pesticides in China. According to the criteria, including the severity of damage caused by pests and the economic value of the crops, the investigated insects, pathogens, herbs and other species in the agricultural field were selected as the main screening targets for pesticides. Corresponding in vivo microscreening methods have been established and applied in the pesticide screening procedure, which has higher reproducibility, a shorter time and greater efficiency that offset the drawbacks of conventional methods for pesticide screening.

Potency and property of DNA conformational damage determine ATM activation: two new DNA topological probes.

We have shown previously the intercalation geometry of a series of acenaphtho [1,2-b] pyrrole derivatives with DNA double helix in vitro. In this report we chose a couple of intercalating analogues and a Chinese traditional medicine Tanshinone IIA as probes to investigate the response of DNA damage sensor ataxia-telangiectasia mutated (ATM) protein toward the DNA topological change in vivo. The two analogues (1)a (3-(4-Methyl-piperazin)-8-oxo-8H-acenaphtho [1,2-b]pyrrole -9-carbonitrile) and (3)a (3-(3-Dimethylamino-propylamino)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9- carbonitrile) could unwind double helix to different extents, whereas Tanshinone IIA could wind the double helix. Using a combination of circular dichroism (CD) studies and immunoflurescence assays, we found for the first time that the ATM protein kinase can respond to the unwinding chromatin conformational damage caused by (1)a and (3)a, while it could not be activated by the winding effects caused by Tanshinone IIA. Moreover, the amount of ATM protein phosphorylation is consistent with the degree of unwinding conformational damage. The average number of ATM foci in an MCF-7 cell is 32 +/- 1.5 at 6 microM (1)a, which is significantly higher than the 8 microM (3)a exposure (15 +/- 0.5, p < 0.5). A new couple of DNA topological probes, (1)a and (3)a have been found for the future semi-quantitative investigation of factors involved in the DNA damage pathway.

Efficient induction of ginsenoside biosynthesis and alteration of ginsenoside heterogeneity in cell cultures of Panax notoginseng by using chemically synthesized 2-hydroxyethyl jasmonate.

Chemically synthesized 2-hydroxyethyl jasmonate (HEJA) was for the first time employed to induce the ginsenoside biosynthesis and to manipulate the product heterogeneity in plant cell cultures. The dose response and timing of HEJA elicitation were investigated in cell suspension cultures of Panax notoginseng. The optimal concentration and timing of HEJA addition for both cell growth and ginsenoside accumulation was identified to be 200 microM added on day 4. It was interestingly found that HEJA could stimulate ginsenosides biosynthesis and change their heterogeneity more efficiently than methyl jasmonate (MJA), i.e., the total ginsenoside content and the Rb/Rg ratio increased about 60 and 30% with HEJA elicitation than that by MJA, respectively. The activity of Rb1 biosynthetic enzyme, i.e., UDPG-ginsenoside Rd glucosyltransferase (UGRdGT), was also higher in the former case. A maximal production titer of ginsenoside Rg1, Re, Rb1, and Rd was 47.4+/-4.8, 52.3+/-4.4, 190+/-18, and 12.1+/-2.5 mg/l with HEJA elicitation, which was about 1.3-, 1.3-, 1.7-, and 2.1-fold than that using MJA, respectively. Early signal events in plant defense response, including oxidative burst and jasmonic acid (JA) biosynthesis, were also examined. Levels of H2O2 and NO in medium and L-phenylalanine ammonia lyase activity in cells were not affected by addition of MJA and HEJA. On the other hand, the JA content in cells was increased with external jasmonates elicitation, and it was inhibited with the addition of JA biosynthesis inhibitors. The results suggest that oxidative burst might not be involved in the jasmonates-elicited signal transduction pathway, and MJA and HEJA may induce the ginsenoside biosynthesis via induction of endogenous JA biosynthesis and key enzymes (such as UGRdGT) in the ginsenoside biosynthetic pathway of P. notoginseng cells. The information is useful for hyperproduction of plant-specific heterogeneous products.

N-aroyloxylthioxo-naphthalimides as DNA photocleavers of aroyloxyl oxygen radicals: synthesis, evaluation, and substituents' effect.

Novel N-Aroyloxylthioxo-naphthalimides as highly efficient 'time-resolved' DNA photocleavers of aroyloxyl radicals type were designed and synthesized. The substituents at the aroyloxyl moiety have an important and unusual influence on the DNA photocleavage, and DNA photodamages of the compounds were unusually not depended on the electronic effects of substituents on the corresponding oxygen-centered radicals. With AM1 semi-empirical quantum calculation, it was found that their photocleaving activities were correlated with the densities of electron clouds on the N-O bonds in the triplet state. N-(m-Dichloro-benzoyloxy)-thioxo-naphthalimide could photodamage DNA effectively at less than the concentration of 2 microM.