Label-free SELEX of aptamers for ultra-sensitive electrochemical aptasensor detection of amanitin in wild mushrooms.

BACKGROUND: Mushroom poisoning poses a significant global health concern, with high morbidity and mortality rates. The primary lethal toxins responsible for this condition are alpha-amanitin (ɑ-AMA) and beta-amanitin (ß-AMA). As a promising bio-recognition molecules in biosensors, aptamers, have been broadly used in the field of food detection. However, the current SELEX-based methods for screening aptamers for structurally similar small molecules were limited by the labelling or salt ion induction. In this study, we aimed to develop a novel label-free SELEX strategy for the screening of aptamers with high affinity and constructed new aptasensors for the detection of ɑ-AMA and ß-AMA. RESULTS: A novel label-free SELEX strategy based on the positively charged gold nanoparticles (AuNPs) was proposed to simultaneous screening of aptamers for ɑ-AMA and ß-AMA. Only 18 rounds of SELEX were required to obtain new aptamers. The candidate aptamers were analyzed by colloidal gold assay, and the sequences of ɑ-30 and ß-37 displayed great affinity with Kd values of 22.26 nM and 23.32 nM, respectively, without interference from botanical toxins. Notably, the truncated aptamers ɑ-30-2 (50 bp) and ß-37-2 (57 bp) exhibited higher affinity than their original counterpart (79 bp). Subsequently, the selected aptamers were utilized to construct recognition probes for electrochemical aptasensors based on hairpin cyclic cleavage of substrates by Cu2+ dependent DNAzyme and Exo I-triggered recycling cascades. The detection platform showed excellent analytical performance with limits of detection as low as 4.57 pg/mL (ɑ-AMA) and 8.49 pg/mL (ß-AMA). Moreover, the aptasensors exhibited superior performance in mushroom and urine samples. SIGNIFICANCE: This work developed a simple and efficient label-free SELEX method for screening new aptamers for ɑ-AMA and ß-AMA, which employed the positively charged AuNPs as the screening medium, without the need for chemical labelling of libraries or induction of salt ions. Furthermore, two novel electrochemical aptasensors were developed based on our newly obtained aptamers, which offer the new biosensing tool for ultrasensitive detection of the AMA poisoning, showing great potential in practical applications.

Prostate cancer stem cells and their targeted therapies.

Prostate cancer (PCa) is the most common malignancy among men worldwide. Through androgen receptor signaling inhibitor (ARSI) treatment, patients eventually succumb to castration-resistant prostate cancer (CRPC). For this, the prostate cancer stem cells (PCSCs), as a minor population of tumor cells that can promote tumor relapse, ARSI resistance, and disease progression, are gaining attention. Therefore, specific therapy targeting PCSCs has momentum. This study reviewed the identification and characterization of PCSCs and PCSC-based putative biomarkers and summarized their mechanisms of action. We further discussed clinical trials of novel therapeutic interventions focused on PCSC-related pathways, the PCSC microenvironment, cutting-edge miRNA therapy, and immunotherapy approaches from a mechanistic standpoint. This review provides updated insights into PCSC plasticity, identifying new PCSC biomarkers and optimized treatments for patients with advanced PCa.

Hexagon AgNCs/PVP Crystallization Induced Cathode Electrochemiluminescence Enhancement for miRNA221 Biosensing.

Aggredation-induced electrochemiluminescence (AIECL) promises an efficient strategy for synthesize highly luminescent emitter and co-reactant for ECL analysis, however, rational control of electrogenerated emission intensity is still challenging. The low electroconductivity and amorphous molecular configuration are intrinsic bottleneck. This work reveals the impact of polyvinyl pyrrolidone backbone regulated silver nanocrystallines (AgNCs/PVP) on the cathode AIECL properties in near infrared region, by employing the Box-Behnken designed response surface computation model to modulate crystal aggregates. Electron paramagnetic resonance spectroscopy discovered hydrogen radical (HO• ) dominant reductive-oxidative (R-O) ECL mechanism with AgNCs acting as the co-reaction accelerator in graphene oxide/persulfate system (GO/S2 O8 2- ). Both theoretical calculation and experimental measurement testified that the ECL of AgNCs in GO/S2 O8 2- dependent on the concentration of in situ electrochemical oxidized Ag+ . The high efficiency of crystallization-induced enhanced ECL (CIECL) originates from 1) the effective electron transfer of Ag+ accelerated HO• produce to notable promote radioactive transition, and 2) twisted intramolecular charge transfer from the electron-rich donor of PVP to electron-deficient receptor of Ag0 to restrict nonradioactive transition. The AgNCs/PVP with CIECL effect are applied to construct an ultrasensitive platform for miR-221 assay with a lower detection limit of 7.47 × 103  copies mL-1 than typical qPCR method.

An electrochemical aptasensor based on target triggered multiple-channel DNAzymes cycling amplification strategy with PtFe@Co-MOF as signal amplifier.

A novel electrochemical aptasensor for the detection of Aflatoxin B1 (AFB1) was developed for the first time by using the target-triggered multiple-channel deoxyribozymes (DNAzymes) cycling amplified assay with Pt Fe doped NH2-Co-MOF (PtFe@Co-MOF) as a signal amplifier. In the presence of AFB1, a self-assembling cross-over nucleic structure could be triggered by AFB1 via two aptamers' structure switching for strand displacement, resulting in four channels of Mg2+-dependent DNAzyme recycling simultaneously to multiply the detection signals. These DNAzymes cyclically split the substrate sequence to release the PtFe@Co-MOF labeled detection probe (DP), which is subsequently hybridized with the capture probes on the Au-deposited glassy carbon electrode. The fabrication procedure was characterized by differential pulse voltammetry, and the results of the morphological and element composition characteristics methods were analyzed to determine the successful preparation of PtFe@Co-MOF. The limit of detection (LOD) for AFB1 detection was 2 pg mL-1 with a linear range from 5 pg mL-1 to 80 ng mL-1. By comparison, the enhanced detection sensitivity has been found to originate from the efficient shearing of DNAzymes, enhanced peroxidase-like capability, and multiple active sites of PtFe@Co-MOF. Besides, this aptasensor showed high specificity for AFB1 compared with similar mycotoxins and exhibited high accuracy with low experimental cost and easy operation. Furthermore, the unique design of electrochemical aptasensors could provide a promising platform for the onsite determination of AFB1, as well as other targets by replacing the aptamer and other core recognition sequences.

Different co-culture models reveal the pivotal role of TBBPA-promoted M2 macrophage polarization in the deterioration of endometrial cancer.

Tetrabromobisphenol A (TBBPA), an emerging organic pollutant widely detected in human samples, has a positive correlation with the development of endometrial cancer (EC), but its underlying mechanisms have not yet been fully elucidated. Tumor-associated macrophages (TAM), one of the most vital components in tumor microenvironment (TME), play regulatory roles in the progression of EC. Consequently, this study mainly focuses on the macrophage polarization in TME to unveil the influence of TBBPA on the progression of EC and involved mechanisms. Primarily, low doses of TBBPA treatment up-regulated M2-like phenotype biomarkers in macrophage. The data from in vitro co-culture models suggested TBBPA-driven M2 macrophage polarization was responsible for the EC deterioration. Results from in vivo study further confirmed the malignant proliferation of EC promoted by TBBPA. Mechanistically, TBBPA-mediated miR-19a bound to the 3'-UTR regions of SOCS1, resulting in down-regulation of SOCS1 followed by the phosphorylation of JAK and STAT6. The present study not only revealed for the first time the molecular mechanism of TBBPA-induced EC's deterioration based on macrophage polarization, but also established co-culture models, thus providing a further evaluation method for the exploration of environmental pollutants-induced tumor effects from the role of TME.

The promotion of tetrabromobisphenol A exposure on Ishikawa cells proliferation and pivotal role of ubiquitin-mediated IκB' degradation.

Tetrabromobisphenol A (TBBPA), one of the highly common industrial brominated flame retardants (BFRs), has been recently reported to influence the progression of endometrial carcinoma. However, the underlying mechanism between them has not been fully illuminated. Our findings demonstrated that treatment with low concentrations of TBBPA significantly induced the proliferation of Ishikawa cells in a concentration- and time-dependent manner. Mechanically, TBBPA stimulation led to the elevation of NF-κB expression, accompanied by the occurrence of ubiquitin-mediated IκB' degradation. Additionally, the upregulation of pro-inflammatory cytokines upon TBBPA exposure was observed in both mRNA and protein levels. Interestingly, the above toxic effects of TBBPA on Ishikawa cells were markedly attenuated by the addition of MG-132, a proteasome inhibitor, suggesting the crucial role of ubiquitin-mediated IκB' degradation in the TBBPA-stimulated proliferation of Ishikawa cells. Confirmation using in vivo model was also presented in this work. Accordingly, our data indicated that ubiquitin-mediated IκB' degradation and inflammatory response could serve as critical and sensitive biomarkers for the TBBPA-induced endometrial carcinoma, which would be helpful for the future carcinogenic risk assessments of TBBPA exposure on uterus.

TBBPA stimulated cell migration of endometrial cancer via the contribution of NOX-generated ROS in lieu of energy metabolism.

Due to the extensive applications and deleterious effects of Tetrabromobisphenol A (TBBPA), the health risk and possible mechanisms have been a topic of concern. However, the knowledge on carcinogenic risk of TBBPA and corresponding mechanisms remains scarce. In this study, endometrial cancer cells were exposed to low doses of TBBPA and its main derivatives including TBBPA bis (2,3-dibromopropyl ether) (TBBPA-BDBPE) and TBBPA bis (2-hydroxyethyl ether) (TBBPA-BHEE). The data from wound healing and transwell assays demonstrated that TBBPA treatment exhibited the strongest enhanced effect on cell migration among other tested treatments. Of note, the process of invasion rather than epithelial-mesenchymal transition (EMT) was accompanied by the occurrence of migration elevated by TBBPA. Furthermore, the levels of several metabolite indicators were measured to assess the underlying mechanisms involved in TBBPA-induced cell migration. The findings suggested that NADPH oxidase (NOX)-driven ROS instead of energy metabolism was sensitive to TBBPA stimulation. In addition, molecular docking supported a link between TBBPA ligand and NOX receptor. Accordingly, this study has provided new insights for TBBPA-induced carcinogenic effects and may arise peoples' vigilance to environmental pollution of brominated flame retardant.

Critical biomarkers for myocardial damage by fine particulate matter: Focused on PPARα-regulated energy metabolism.

Fine particulate matter is one of the leading threats to cardiovascular health worldwide. The exploration of novel and sensitive biomarkers to detect damaging effect of fine particulate matter on cardiac tissues is of great importance in the better understanding of haze-caused myocardial injury. A link between heart failure and PPARα-regulated energy metabolism has been confirmed previously. Herein, the study intends to reveal the critical biomarkers of fine particulate matter induced myocardial damage from the PPARα-regulated energy metabolism. Ambient fine particulate matter induced severe pathological alterations in cultured cells, accompanied by the decrease in ATP content. Additionally, the expressions of CPT1/CPT2 and levels of CS and MDH, crucial members in ß-oxidation and the TCA cycle, were significantly decreased. In direct contrast, fine particulate matter increased the biomarkers of glycolysis, as measured by the accumulation of pyruvate and lactate contents, and the enhanced activities of HK and PKM1/2. Importantly, fine particulate matter-exposed cardiomyocytes exhibited the reduced PPARα level, that increased when cardiomyocytes were co-incubation with WY-14643 and fine particulate matter. Simultaneously, the adverse impact of fine particulate matter on critical biomarkers were observed in ß-oxidation, TCA cycle and glycolysis, associated with WY-14643 additional complement. Fine particulate matter caused the myocardial energy metabolism transformation through the regulation of PPARα expression and translation, which provided novel and critical biomarkers for haze particles-caused myocardial damage.

TBBPA regulates calcium-mediated lysosomal exocytosis and thereby promotes invasion and migration in hepatocellular carcinoma.

Tetrabromobisphenol A (TBBPA) and its derivatives are the common flame-retardants that may increase the risk of development of many types of cancers, including liver cancer. However, the effects of TBBPA in the development and progression of liver cancer remains unknown. This study investigated the potential effects of TBBPA on a metastatic phenotype of hepatocellular carcinoma cell line-HepG2. Our results revealed that TBBPA significantly promoted the migration and invasion via affecting the number and distribution of lysosomes in HepG2 cells in a dose-dependent manner. Moreover, TBBPA decreased the intracellular protein levels of Beta-Hexosaminidase (HEXB), Cathepsin B (CTSB) and Cathepsin D (CTSD) while increased the extracellular CTSB and CTSD. It entailed that TBBPA exposure could promote the lysosomal exocytosis in cancer cells. The reversal results were obtained after adding lysosomal exocytosis inhibitor vacuolin-1. Docking results suggested that TBBPA could bind to TRPML1. It was consistent with the binding position of agonist ML-SA1. TRPML1 knockdown significantly decreased the invasion and migration, and the results were reversed when TBBPA was added. The results were indicated that TRPML1 was critical in lysosomal exocytosis. In addition, our results showed that TBBPA-TRPML1 complex regulated the calcium-mediated lysosomal exocytosis, thereby promoting the metastasis in liver cancer cells. It was expected that our data could provide important basis for understanding the molecular mechanism(s) of TBBPA promoting invasion and migration of hepatoma cells and give rise to profound concerns of TBBPA exposure on human health.

3D-Structured Carbonized Sunflower Heads for Improved Energy Efficiency in Solar Steam Generation.

Solar steam generation is regarded as a perspective technology, due to its potentials in solar light absorption and photothermal conversion for seawater desalination and water purification. Although lots of steam generation systems have been reported to possess high conversion efficiencies recently, researches of simple, cost-effective, and sustainable materials still need to be done. Here, inspired by natural young sunflower heads' property increasing the temperature of dish-shaped flowers by tracking the sun, we used 3D-structured carbonized sunflower heads as an effective solar steam generator. The evaporation rate and efficiency of these materials under 1 sun (1 kW m-2) are 1.51 kg m-2 h-1 and 100.4%, respectively, beyond the theoretical limit of 2D materials. This high solar efficiency surpasses all other biomass-based materials ever reported. It is demonstrated that such a high capability is mainly attributed to the 3D-structured top surface, which could reabsorb the lost energy of diffuse reflection and thermal radiation, as well as provide enlarged water/air interface for steam escape. 3D-structured carbonized sunflower heads provide a new method for the future design and fabrication of high-performance photothermal devices.

In situ synthesis of BiOCl nanosheets on three-dimensional hierarchical structures for efficient photocatalysis under visible light.

Assembling two-dimensional (2D) nanomaterials into three-dimensional (3D) hierarchical structures with novel functions is challenging and has attracted considerable attention. However, it is quite difficult to obtain complex 3D architectures of 2D materials with a uniform and intact structure using traditional methods, such as hydrothermal/solvothermal methods and direct precipitation methods. Here, we use butterfly wing scales as bio-templates to prepare 3D hierarchical BiOCl/Au wing scales for plasmonic photocatalysis. The as-prepared materials exhibit excellent photodegradation of rhodamine B (RhB) under visible light. The degradation rates of BiOCl microspheres and BiOCl and BiOCl/Au butterfly wing scales are 48.8%, 72.6%, and 93.8%, respectively, within 20-min illumination at the same loading capacities. This excellent performance of BiOCl/Au is attributed to the coupling of enhanced carrier separation efficiency and the effect of localized surface plasmon resonance (LSPR) aroused by 3D metallic structures. This study provides a relatively facile method to obtain complex 3D constructure of 2D materials. It also demonstrates a nature-led route to prepare highly efficient plasmonic photocatalysts.

Tumor Chemo-Radiotherapy with Rod-Shaped and Spherical Gold Nano Probes: Shape and Active Targeting Both Matter.

The morphologies of gold nanoparticles (NPs) affect their tumor accumulation through enhanced permeability and retention effect. However, detailed information and mechanisms of NPs' characteristics affecting tumor accumulation are limited. The aim of this study is to evaluate the effects of shape and active targeting ligands of theranostic NPs on tumor accumulation and therapeutic efficacy, and to elucidate the underlying mechanism. Methods:αvß3 integrin-targeted, cisplatin-loaded and radioisotope iodine-125 labeled spherical and rod-shaped gold nano theranostic probes (RGD-125IPt-AuNPs and RGD-125IPt-AuNRs) with similar sizes were fabricated and characterized. The in vivo distribution and chemo-radio therapeutic efficacy against tumors of these newly developed probes were subsequently evaluated. Moreover, a physiologically based pharmacokinetic (PBPK) model was developed to characterize the in vivo kinetics of these probes at the sub-organ level, and to reveal the mechanism of NPs' shape and active targeting ligands effects on tumor accumulation. Result: Cisplatin and iodine-125 were loaded sequentially onto the NPs through a thin polydopamine coating layer on the NPs. Both RGD-125IPt-AuNPs and RGD-125IPt-AuNRs exhibited high specificity for αvß3 in vitro, with the rod-shaped probe being more efficient. The PBPK model revealed that rod-shaped gold NPs diffused more rapidly in tumor interstitial than the spherical ones. Tumor accumulations of non-targeted and rod-shaped RAD-125IPt-AuNRs was higher in short term (1 h post injection), but not pronounced and similar to that of non-targeted spherical RAD-125IPt-AuNPs in 24 h after intravenous injection, revealing that the NPs' shape did not have a significant impact on tumor accumulations through enhanced permeability and retention (EPR) effect in long-term. While for actively targeted NPs, in addition to a higher distribution coefficient, RGD-125IPt-AuNRs also had a much higher tumor maximum uptake rate constant than RGD-125IPt-AuNPs, indicating both the shape and active targeting ligands affected the tumor uptake of rod-shaped NPs. As a result, RGD-125IPt-AuNRs had a more effective inhibition of tumor growth than RGD-125IPt-AuNPs by chemo-radiationtherapy. Conclusion: Our study suggests that both the shape and active targeting ligands of gold NPs play important roles on tumor accumulation and chemo-radio therapeutic effect.

GE11-PDA-Pt@USPIOs nano-formulation for relief of tumor hypoxia and MRI/PAI-guided tumor radio-chemotherapy.

Radio-chemo combination therapy has synergetic therapeutic effects on tumors. However, the tumor microenvironment, e.g. hypoxia and elevated H2S levels, limits its treatment efficacy. In this study, we developed a cisplatin-loaded, poly dopamine-coated and GE11 peptide-conjugated multi-functional theranostic system (GE11-PDA-Pt@USPIOs) based on poly acrylic acid-coated ultra-small superparamagnetic iron oxide nanoparticles (PAA@USPIOs) for modulation of the tumor hypoxic microenvironment and magnetic resonance imaging/photoacoustic imaging (MRI/PAI) guided radio-chemotherapy of tumors. The thick PAA coating on the USPIOs allowed highly efficient cisplatin loading by complexing the carboxylic groups on PAA with activated cisplatin. A subsequent thin layer of polydopamine (PDA) encapsulation following drug loading provided a means of further surface functionalization; it endowed the particles with photo-thermal properties but did not impede release of the drug or iron ions. GE11-PDA-Pt@USPIOs had high specificity for EGFR-positive tumor cells, could catalyze decomposition of H2O2 to oxygen and exhibited radio-chemo synergetic therapeutic effects under hypothermia conditions in vitro. Once administered intravenously, MRI and PA imaging revealed that the probes were able to accumulate in tumors with high efficiency; this relieved the tumor hypoxic conditions, sensitizing the tumors to radiation therapy. As a result, radio-chemo combination therapy significantly inhibited tumor growth. Our study illustrates for the first time that USPIOs can relieve tumor hypoxia and that GE11-PDA-Pt@USPIOs are highly effective for radio-chemotherapy of EGFR-positive tumors.

Exposure to ambient fine particles causes abnormal energy metabolism and ATP decrease in lung tissues.

Airborne fine particles, generating from human activities, have drawn increasing attention due to their potential lung health hazards. The currently available toxicological data on fine particles is still not sufficient to explain their cause-and-effect. Based on well reported critical role of ATP on maintaining lung structure and function, the alterations of ATP production and energy metabolism in lungs of rats exposed to different dosages of seasonal PM2.5 were investigated. Haze dosage PM2.5 exposure was demonstrated to reduce the ATP production. Activity of critical enzymes in TCA cycle, such as malate dehydrogenase (MDH) and citrate synthase (CS), and expression of mitochondrial respiration chain genes were attenuated in groups exposed to haze dosage PM2.5. In contrast, there was prominent augment of glycolytic markers at haze dosage PM2.5, including metabolite contents (pyruvate and lactic acid), enzyme activities (hexokinase (HK) and pyruvate kinase (PKM)), along with mRNA levels of PKM and LDH. Consequently, sub-chronic exposure to seasonal haze PM2.5 caused reduction in ATP generation and metabolic rewiring from TCA cycle to glycolysis. Our findings can help better understand the toxicological mechanism of lung disease caused by particulate air pollution.

Sensitive detection of MCF-7 human breast cancer cells by using a novel DNA-labeled sandwich electrochemical biosensor.

The simple, rapid, sensitive, and specific detection of cancer cells plays a pivotal role in the diagnosis and prognosis of cancer. We developed a novel DNA-labeled sandwich electrochemical biosensor based on a glassy carbon electrode modified with 3D graphene and a hybrid of Au nanocages (Au NCs)/amino-functionalized multiwalled carbon nanotubes (MWCNT-NH2) for label-free and selective detection of MCF-7 breast cancer cells via differential pulse voltammetry. The layer-by-layer assembly and cell-detection performance of the Au NCs/MWCNTs-NH2-based biosensor were investigated using scanning electron microscopy and electrochemical methods including cyclic voltammetry and electrochemical impedance spectroscopy. Owing to the advantages of DNA-labeled antibodies and a nanomaterial-based signal amplification strategy, the fabricated cytosensor exhibited high specificity and sensitivity when detecting MCF-7 cells in the range of 1.0 × 102 to 1.0 × 106 cells mL-1 with a low detection limit of 80 cells mL-1 (3σ/slope). Furthermore, the biosensor exhibited high selectivity when detecting MCF-7 cells and showed considerable potential for practical applications. The proposed DNA-labeled sandwich electrochemical biosensor provides a stable, sensitive approach to detecting cancer cells and is promising in terms of potential applications to cancer diagnosis.

Ordering of Hollow Ag-Au Nanospheres with Butterfly Wings as a Bio-template.

A biological template strategy is implemented for the fabrication of hollow noble metal composite nanospheres within the ordered array nanostructures by introducing butterfly wings to some convenient technique procedure. Butterfly wings are activated by ethylenediamine to increase the reactive sites on the chitin component, on which Ag nanoparticles are in situ formed and serve as "seeds" to direct further incorporation during the following impregnation procedure. Butterfly wings could function as bio-substrate to provide an ordered array and regulate the synthesis process by providing active reaction sites (e.g. -CONH- and -OH). Thus, hollow Ag-Au nanospheres are loaded on the wings' surface layer and inside the ordered array nanostructures homogeneously, which would have potential applications in surface enhanced Raman scattering (SERS).

Three-Dimensional CdS/Au Butterfly Wing Scales with Hierarchical Rib Structures for Plasmon-Enhanced Photocatalytic Hydrogen Production.

Localized surface plasmon resonance (LSPR) of plasmonic metals (e.g., Au) can help semiconductors improve their photocatalytic hydrogen (H2) production performance. However, an artificial synthesis of hierarchical plasmonic structures down to nanoscales is usually difficult. Here, we adopt the butterfly wing scales from Morpho didius to fabricate three-dimensional (3D) CdS/Au butterfly wing scales for plasmonic photocatalysis. The as-prepared materials well-inherit the pristine hierarchical biostructures. The 3D CdS/Au butterfly wing scales exhibit a high H2 production rate (221.8 µmol·h-1 within 420-780 nm), showing a 241-fold increase over the CdS butterfly wing scales. This is attributed to the effective potentiation effect of LSPR introduced by multilayer metallic rib structures and a good interface bonding state between Au and CdS nanoparticles. Thus, our study provides a relatively simple method to learn from nature and inspiration for preparing highly efficient plasmonic photocatalysts.

Dual Chemodrug-Loaded Single-Walled Carbon Nanohorns for Multimodal Imaging-Guided Chemo-Photothermal Therapy of Tumors and Lung Metastases.

Tumor combination therapy using nano formulations with multimodal synergistic therapeutic effects shows great potential for complete ablation of tumors. However, targeting tumor metastases with nano structures is a major obstacle for therapy. Therefore, developing a combination therapy system able to target both primary tumors and their metastases at distant sites with synergistic therapy is desirable for the complete eradication of tumors. To this end, a dual chemodrug-loaded theranostic system based on single walled carbon nanohorns (SWNHs) is developed for targeting both primary breast tumors and their lung metastases. Methods: SWNHs were first modified simultaneously with poly (maleic anhydride-alt-1-octadecene) (C18PMH) and methoxypolyethyleneglycol-b-poly-D, L-lactide (mPEG-PLA) via hydrophobic-hydrophobic interactions and π-π stacking. Then cisplatin and doxorubicin (DOX) (2.9:1 molar ratio) were sequentially loaded onto the modified nanohorns in a noninterfering way. After careful examinations of the release profiles of the loaded drugs and the photothermal performance of the dual chemodrug-loaded SWNHs, termed SWNHs/C18PMH/mPEG-PLA-DOX-Pt, the dual drug chemotherapeutic and chemo-photothermal synergetic therapeutic effects on tumor cells were evaluated. Subsequently, the in vivo behavior and tumor accumulation of the drug-loaded SWNHs were studied by photoacoustic imaging (PAI). For chemo-photothermal therapy of tumors, 4T1 tumor bearing mice were intravenously injected with SWNHs/C18PMH/mPEG-PLA-DOX-Pt at a dose of 10 mg/kg b.w. (in SWNHs) and tumors were illuminated by an 808 nm laser (1W/cm2 for 5 min) 24 h post-injection. Results: DOX and cisplatin were loaded onto the modified SWNHs with high efficiency (44 wt% and 66 wt%, respectively) and released in a pH-sensitive, tandem and sustainable manner. The SWNHs/C18PMH/mPEG-PLA-DOX-Pt had a hydrodynamic diameter of 182 ± 3.2 nm, were highly stable in physiological environment, and had both dual drug chemotherapeutic (CI = 0.439) and chemo-photothermal synergistic antitumor effects (CI = 0.396) in vitro. Moreover, the dual drug-loaded SWNHs had a long blood half-life (10.9 h) and could address both the primary breast tumors and their lung metastases after intravenous administration. Consequently, chemo-photothermal combination therapy ablated the primary tumors and simultaneously eradicated the metastatic lung nodules. Conclusion: Our study demonstrates that SWNHs/C18PMH/mPEG-PLA-DOX-Pt is highly potent for chemo-photothermal combination therapy of primary tumors and cocktail chemotherapy of their metastases at a distant site.

Quantum Dots of 1T Phase Transitional Metal Dichalcogenides Generated via Electrochemical Li Intercalation.

We prepare group VI transitional metal dichalcogenides (TMDs, or MX2) from the 1T phase with quantum-sized and monolayer features via a quasi-full electrochemical process. The resulting two-dimensional (2D) MX2 (M = W, Mo; X = S, Se) quantum dots (QDs) are ca. 3.0-5.4 nm in size with a high 1T phase fraction of ca. 92%-97%. We attribute this to the high Li content intercalated in the 1T-MX2 lattice (mole ratio of Li:M is over 2:1), which is achieved by an increased lithiation driving force and a reduced electrochemical lithiation rate (0.001 A/g). The high Li content not only promotes the 2H → 1T phase transition but also generates significant inner stress that facilitates lattice breaking for MX2 crystals. Because of their high proportion of metallic 1T phase and sufficient active sites induced by the small lateral size, the 2D 1T-MoS2 QDs show excellent hydrogen evolution reactivity (with a typical η10 of 92 mV, Tafel slope of 44 mV/dec, and J0 of 4.16 × 10-4 A/cm2). This electrochemical route toward 2D QDs might help boost the development of 2D materials in energy-related areas.

Angle-independent pH-sensitive composites with natural gyroid structure.

pH sensor is an important and practical device with a wide application in environmental protection field and biomedical industries. An efficient way to enhance the practicability of intelligent polymer composed pH sensor is to subtilize the three-dimensional microstructure of the materials, adding measurable features to visualize the output signal. In this work, C. rubi wing scales were combined with pH-responsive smart polymer polymethylacrylic acid (PMAA) through polymerization to achieve a colour-tunable pH sensor with nature gyroid structure. Morphology and reflection characteristics of the novel composites, named G-PMAA, are carefully investigated and compared with the original biotemplate, C. rubi wing scales. The most remarkable property of G-PMAA is a single-value corresponding relationship between pH value and the reflection peak wavelength (λmax), with a colour distinction degree of 18 nm/pH, ensuring the accuracy and authenticity of the output. The pH sensor reported here is totally reversible, which is able to show the same results after several detection circles. Besides, G-PMAA is proved to be not influenced by the detection angle, which makes it a promising pH sensor with superb sensitivity, stability, and angle-independence.