A Green Synthesis of Au-Ag Alloy Nanoparticles using Polydopamine Chemistry: Evaluation of their Anticancer Potency Towards Both MCF-7 Cells and their Cancer Stem Cells Subgroup.

BACKGROUND: Limited chemotherapy efficacy and cancer stem cells (CSCs)-induced therapeutic resistance are major difficulties for tumour treatment. Adopting more efficient therapies to eliminate bulk-sensitive cancer cells and resistant CSCs is urgently needed. METHODS: Based on the potential and functional complementarity of gold and silver nanoparticles (AuNPs or AgNPs) on tumour treatment, bimetallic NPs (alloy) have been synthesized to obtain improved or even newly emerging bioactivity from a combination effect. This study reported a facile, green and economical preparation of Au-Ag alloy NPs using biocompatible polydopamine (PDA) as a reductant, capping, stabilizing and hydrophilic agent. RESULTS: These alloy NPs were quasi-spherical with rough surfaces and recorded in diameters of 80 nm. In addition, these alloy NPs showed good water dispersity, stability and photothermal effect. Compared with monometallic counterparts, these alloy NPs demonstrated a dramatically enhanced cytotoxic/pro-apoptotic/necrotic effect towards bulk-sensitive MCF-7 and MDA-MB-231 cells. The underlying mechanism regarding the apoptotic action was associated with a mitochondria-mediated pathway, as evidenced by Au3+/Ag+ mediated Mitochondria damage, ROS generation, DNA fragmentation and upregulation of certain apoptotic-related genes (Bax, P53 and Caspase 3). Attractively, these Au-Ag alloy NPs showed a remarkably improved inhibitory effect on the mammosphere formation capacity of MCF-7 CSCs. CONCLUSION: All the positive results were attributed to incorporated properties from Au, Ag and PDA, the combination effect of chemotherapy and photothermal therapy and the nano-scaled structure of Au-Ag alloy NPs. In addition, the high biocompatibility of Au-Ag alloy NPs supported them as a good candidate in cancer therapy.

Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner.

The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.

A New Gold Nanoparticles and Paclitaxel Co-Delivery System for Enhanced Anti-Cancer Effect Through Chemo-Photothermal Combination.

Limited chemotherapeutic efficiency, drug resistance and side effect are primary obstacles for cancer treatment. The development of co-delivery system with synergistic treatment modes should be a promising strategy. Here, we fabricated a multi-functionalized nanocarrier with a combination of chemotherapeutic agent and gold nanoparticles (AuNPs), which could integrate chemo-photothermal therapy and improve entire anti-cancer index. Particularly, Paclitaxel nanocrystals (PTX NC) were first fabricated as a platform, on surface of which AuNPs were decorated and polydopamine (PDA) layer act as capping, stabilizing and hydrophilic agents for PTX NC, providing a bridge connecting AuNPs to PTX. These AuNPs decorated PTX NC exhibited good physico-chemical properties like optimal sizes, stability and photothermal efficiency. Compared to other PTX formulations, they displayed considerably improved biocompatibility, selectivity, intracellular uptake, cytotoxicity, apoptosis induction activity and P-glycoprotein (Pgp) inhibitory capability, owing to a synergistic/ cooperative effect from AuNPs, PTX and NIR treatment, photothermal-triggered drug release and nano-scaled structure. Mitochondria-mediated signaling pathway is underlying mechanism for cytotoxic and apoptotic effect from AuNPs decorated PTX NC, in terms of Mitochondria damage, a loss of Mitochondrial membrane potential, intensified oxidative stress, DNA breakage, Caspase 3 activation, up-regulated expression in pro-apoptotic genes like p53, Caspase 3 and Bax and down-regulated level in anti-apoptotic gene like Bcl-2.

Gold Nanoparticle-Decorated Drug Nanocrystals for Enhancing Anticancer Efficacy and Reversing Drug Resistance Through Chemo-/Photothermal Therapy.

Limited chemotherapeutic efficiency, drug resistance, and side effects are primary obstacles for cancer treatment. The development of co-delivery systems with synergistic treatment modes should be a promising strategy. Here, we fabricated a multifunctionalized nanocarrier with a combination of chemotherapeutic agents and gold nanoparticles (AuNPs), which could integrate chemo-photothermal therapy, thus enhancing overall anticancer efficacy, sensitizing drug-resistant cancer cells, and diminishing cancer stem cells (CSCs). To be specific, camptothecin nanocrystals (CPT NCs) were prepared as a platform, on the surface of which AuNPs were decorated and a hyaluronic acid layer acted as capping, stabilizing, targeting, and hydrophilic agents for CPT NCs, and reducing agents for AuNPs, providing a bridge connecting AuNPs to CPT. These AuNP-decorated CPT NCs exhibited good physico-chemical properties such as optimal sizes, payload, stability, and photothermal efficiency. Compared to other CPT formulations, they displayed considerably improved biocompatibility, selectivity, intracellular uptake, cytotoxicity, apoptosis induction activity, Pgp inhibitory capability, and anti-CSC activity, owing to a synergistic/cooperative effect from AuNPs, CPT, near-infrared treatment, pH/photothermal-triggered drug release, and nanoscaled structure. A mitochondrial-mediated signaling pathway is the underlying mechanism for cytotoxic and apoptotic effects from AuNP-decorated CPT NCs, in terms of mitochondrial dysfunction, intensified oxidative stress, DNA fragmentation, caspase 3 activation, upregulation of proapoptotic genes such as p53, Bax, and caspase 3, and lower levels of antiapoptotic Bcl-2.

Hyaluronic Acid-Coated Camptothecin Nanocrystals for Targeted Drug Delivery to Enhance Anticancer Efficacy.

Tumor-targeted drug delivery via chemotherapy is very effective on cancer treatment. For potential anticancer agent such as Camptothecin (CPT), high chemotherapeutic efficacy and accurate tumor targeting are equally crucial. Inspired by special CD44 binding capability from hyaluronic acid (HA), in this study, novel HA-coated CPT nanocrystals were successfully prepared by an antisolvent precipitation method for tumor-targeted delivery of hydrophobic drug CPT. These HA-coated CPT nanocrystals demonstrated high drug loading efficiency, improved aqueous dispersion, prolonged circulation, and enhanced stability resulting from their nanoscaled sizes and hydrophilic HA layer. Moreover, as compared to crude CPT and naked CPT nanocrystals, HA-coated CPT nanocrystals displayed dramatically enhanced in vitro anticancer activity, apoptosis-inducing potency against CD44 overexpressed cancer cells, and lower toxic effect toward normal cells due to pH-responsive drug release behavior and specific HA-CD44 mediated endocytosis. Additionally, HA-coated CPT nanocrystals performed fairly better antimigration activity and biocompatibility. The possible molecular mechanism regarding this novel drug formulation might be linked to intrinsic mitochondria-mediated apoptosis by an increase of Bax to Bcl-2 ratio and upregulation of P53. Consequently, HA-coated CPT nanocrystals are expected to be an effective nanoplatform in drug delivery for cancer therapy.

Discriminating the Mineralogical Composition in Drill Cuttings Based on Absorption Spectra in the Terahertz Range.

Understanding the geological units of a reservoir is essential to the development and management of the resource. In this paper, drill cuttings from several depths from an oilfield were studied using terahertz time domain spectroscopy (THz-TDS). Cluster analysis (CA) and principal component analysis (PCA) were employed to classify and analyze the cuttings. The cuttings were clearly classified based on CA and PCA methods, and the results were in agreement with the lithology. Moreover, calcite and dolomite have stronger absorption of a THz pulse than any other minerals, based on an analysis of the PC1 scores. Quantitative analyses of minor minerals were also realized by building a series of linear and non-linear models between contents and PC2 scores. The results prove THz technology to be a promising means for determining reservoir lithology as well as other properties, which will be a significant supplementary method in oil fields.

Real-time detection of dielectric anisotropy or isotropy in unconventional oil-gas reservoir rocks supported by the oblique-incidence reflectivity difference technique.

Current geological extraction theory and techniques are very limited to adequately characterize the unconventional oil-gas reservoirs because of the considerable complexity of the geological structures. Optical measurement has the advantages of non-interference with the earth magnetic fields, and is often useful in detecting various physical properties. One key parameter that can be detected using optical methods is the dielectric permittivity, which reflects the mineral and organic properties. Here we reported an oblique-incidence reflectivity difference (OIRD) technique that is sensitive to the dielectric and surface properties and can be applied to characterization of reservoir rocks, such as shale and sandstone core samples extracted from subsurface. The layered distribution of the dielectric properties in shales and the uniform distribution in sandstones are clearly identified using the OIRD signals. In shales, the micro-cracks and particle orientation result in directional changes of the dielectric and surface properties, and thus, the isotropy and anisotropy of the rock can be characterized by OIRD. As the dielectric and surface properties are closely related to the hydrocarbon-bearing features in oil-gas reservoirs, we believe that the precise measurement carried with OIRD can help in improving the recovery efficiency in well-drilling process.

Reproductive toxicity of brazilein in ICR mice.

Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.

[Regulatory effects of Wuzhuyutang (Evodiae prescription) and its consisting herbs on TPH2 promoter].

OBJECTIVE: To screen the active component of Wuzhuyutang (WZYT, Evodiae prescription) and investigate the regulatory effects of the components in WZYT on the TPH2 promoter, and to explore the possible molecular mechanism of WZYT on migraine. METHOD: By transfecting a TPH2 promoter regulating Red Fluorescent Protein expressing plasmid into PC12 cell, the global fluorescence intensities and calculations of fluorescent cells after components treatment were statistically evaluated. RESULT: Different regulatory effects of different components in WZYT with different concentrations on TPH2 promoter were observed. CONCLUSION: TPH2 promoter drove Red Fluorescent Protein expressing cell line can be used as system screening components targeting TPH2 promoter activity. The possible mechanism of WZYT on migraine may due to its stimulating effects on TPH2 promoter, and promote the synthesis and release of 5-HT in cerebral.