Correction: Tumor-targeting, enzyme-activated nanoparticles for simultaneous cancer diagnosis and photodynamic therapy.

Correction for 'Tumor-targeting, enzyme-activated nanoparticles for simultaneous cancer diagnosis and photodynamic therapy' by Huaxia Shi et al., J. Mater. Chem. B, 2016, 4, 113-120, https://doi.org/10.1039/C5TB02041G.

Amyloid Cascade Hypothesis for the Treatment of Alzheimer's Disease: Progress and Challenges.

The amyloid cascade hypothesis has always been a research focus in the therapeutic field of Alzheimer's disease (AD) since it was put forward. Numerous researchers attempted to find drugs for AD treatment based on this hypothesis. To promote the research of anti-AD drugs development, the current hypothesis and pathogenesis were reviewed with expounding of ß-amyloid generation from its precursor protein and related transformations. Meanwhile, the present drug development strategies aimed at each stage in this hypothesis were also summarized. Several strategies especially immunotherapy showed the optimistic results in clinical trials, but only a small percentage of them eventually succeeded. In this review, we also tried to point out some common problems of drug development in preclinical and clinical studies which might be settled through multidisciplinary cooperation as well as the understanding that reinforces the amyloid cascade hypothesis.

A photoelectrochemical sensor based on a reliable basic photoactive matrix possessing good analytical performance for miRNA-21 detection.

The basic photoactive matrixes on transparent electrodes are essential for the performance of photoelectrochemical (PEC) biosensors. Herein, we demonstrate an optimized fabrication strategy toward a reliable ITO/TiO2/AuNP photoanode by sequential deposition of TiO2/Au nanoparticles (Au NPs) on indium tin oxide (ITO) substrates. The identified fabrication conditions include spin-coating tetraisopropyl titanate on ITO slices followed by in situ electrodeposition of Au NPs and finally the thermal annealing treatment. By the conjugation of the thiolated hairpin NH2-DNA sequence and CdTe quantum dots (QDs) onto the thus-prepared photoanodes, a novel PEC sensor for the ultrasensitive detection of miRNA was constructed. The proposed PEC sensor offered advantages including simple structure, storage stability and excellent detection reproducibility as well as sensitivity and specificity toward miRNA-21. Finally, we found that this PEC displayed a broad detection linear range of 1.0 fM to 1.0 nM with a low detection limit of 0.37 fM. This PEC sensor can also excellently discriminate the mismatched miRNA. Moreover, the PEC sensor also showed a satisfactory result in normal human serum sample analysis. These findings emphasized the importance of basic photoactive matrixes for the fabrication of PEC sensors, providing solid fundamental insights for future application of metal oxide substrates for other PEC applications, especially PEC biosensors.

A lipase-responsive antifungal nanoplatform for synergistic photodynamic/photothermal/pharmaco-therapy of azole-resistant Candida albicans infections.

A lipase-triggered drug release nanoplatform (PGL-DPP-FLU NPs) for multi-modal antifungal therapy is developed. The lipases secreted by C. albicans can accelerate FLU release. The ROS and heat produced by PGL-DPP-FLU NPs make C. albicans more vulnerable to FLU, thereby PGL-DPP-FLU NPs exhibit high performance for combating azole-resistant C. albicans biofilms and wound infection.

Au nanoparticles on two-dimensional MoS2 nanosheets as a photoanode for efficient photoelectrochemical miRNA detection.

MiRNAs are small regulatory RNAs that play crucial roles in the oncogenic state in various cancers and have shown highly promising clinical applications as plasma-based markers for cancer classification and prognostication. Due to their electroanalytical advantages, photoelectrochemical biosensors are a very attractive alternative technology for miRNA sensing and detection. In this work, we demonstrated a novel photoelectrochemical (PEC) sensor using the in situ grown Au nanoparticles/two-dimensional molybdenum disulfide (MoS2) nanosheet heterojunction (MoS2-AuNPs) on ITO glass as the photoanode (MoS2-AuNPs/ITO). AuNPs were used as a photoelectronic transfer promoter and DNA probe immobilization carrier as well. The thiol modified biotin DNA with a hairpin structure was tethered to the MoS2-AuNPs/ITO surface to form a specific capturing layer for miRNA detection. The biotin specific protein streptavidin was used as the signal amplifying species. This PEC sensor is structurally simple and possesses sensitivity and specificity toward miRNA. The CV and EIS responses were evaluated to monitor the PEC anode fabrication. The stability and reproducibility of this PEC design strategy were both evaluated before it was used in analyzing the samples of miRNA in human serum. Finally, we found that this PEC sensor displayed a broad detection linear range and a low detection limit of 4.21 fM, and it can excellently discriminate the mismatched miRNA. These findings pave the way for developing PEC sensors targeting miRNA by using noble metals/MoS2 heterojunctions.

NIR-Absorbing water-soluble conjugated polymer dots for photoacoustic imaging-guided photothermal/photodynamic synergetic cancer therapy.

"Theranostics" become increasingly significant in current personalized precision medicine. Herein, we developed a new NIR-absorbing photo-theranostic agent based on water-soluble diketopyrrolopyrrole (DPP) conjugated polymer (WSCP) dots. The WSCPs can be easily self-assembled into WSCP dots under ultrasonication only, instead of any other nano-technology. Compared to the monomers of WSCPs, WSCP dots have no fluorescence emission but produce photoacoustic (PA) signal detected upon laser irradiation due to the reduced energy loss from excited state. PA imaging in vivo indicated that WSCP dots can accumulate at tumor site within 4 h post-injection. More importantly, WSCP dots not only generate heat with a photothermal conversion efficiency of ∼54%, but also produce reactive oxygen species (ROS, QY ∼13%). Furthermore, in vitro and in vivo experiments confirmed effective inhibition of tumor growth by WSCP dots via synergetic photothermal/photodynamic therapy. All results indicate a great potential of WSCP dots as highly efficient theranostic agents in PA imaging-guided synergetic cancer treatment.

Efficient click chemistry towards fatty acids containing 1,2,3-triazole: Design and synthesis as potential antifungal drugs for Candida albicans.

Candida is an important opportunistic human fungal pathogen. The cis-2-dodecenoic acid (BDSF) showing in vitro activity of against C. albicans growth, germ-tube germination and biofilm formation has been a potential inhibitor for Candida and other fungi. In this study, facile synthetic strategies toward a novel family of BDSF analogue, 1-alkyl-1H-1,2,3-triazole-4-carboxylic acids (ATCs) was developed. The straightforward synthetic method including converting the commercial available alkyl bromide to alkyl azide, consequently with a typical click chemistry method, copper(II) sulfate and sodium ascorbate as catalyst in water to furnish ATCs with mild to good yields. According to antifungal assay, 1-decyl-4,5-dihydro-1H-1,2,3-triazole-4-carboxylic acid (5d) showed antifungal capability slightly better than BDSF. The 1,2,3-triazole unit played a crucial role for the bioactivity of ATCs was also confirmed when compared with two alkyl-aromatic carboxylic acids. Given its simplicity, high antifungal activity, and wide availability of compounds with halide atoms on the end part of the alkyl chains, the method can be extended to develop more excellent ATC drugs for accomplishing the challenges in future antifungal applications.

Thermally Activated Delayed Fluorescence Organic Dots (TADF Odots) for Time-Resolved and Confocal Fluorescence Imaging in Living Cells and In Vivo.

The fluorophores with long-lived fluorescent emission are highly desirable for time-resolved fluorescence imaging (TRFI) in monitoring target fluorescence. By embedding the aggregates of a thermally activated delayed fluorescence (TADF) dye, 2,3,5,6-tetracarbazole-4-cyano-pyridine (CPy), in distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) matrix, CPy-based organic dots (CPy-Odots) with a long fluorescence lifetime of 9.3 µs (in water at ambient condition) and high brightness (with an absolute fluorescence quantum efficiency of 38.3%) are fabricated. CPy-Odots are employed in time-resolved and confocal fluorescence imaging in living Hela cells and in vivo. The green emission from the CPy-Odots is readily differentiated from the cellular autofluorescence background because of their stronger emission intensities and longer lifetimes. Unlike other widely studied DSPE-PEG2000 encapsulated Odots which are always distributed in cytoplasm, CPy-Odots are located mainly in plasma membrane. In addition, the application of CPy-Odots as a bright microangiography agent for TRFI in zebrafish is also demonstrated. Much broader application of CPy-Odots is also prospected after further surface functionalization. Given its simplicity, high fluorescence intensity, and wide availability of TADF materials, the method can be extended to develop more excellent TADF Odots for accomplishing the challenges in future bioimaging applications.

A Conjugated Polyelectrolyte with Pendant High Dense Short-Alkyl-Chain-Bridged Cationic Ions: Analyte-Induced Light-Up and Label-Free Fluorescent Sensing of Tumor Markers.

A novel cationic water-soluble conjugated polyelectrolyte (CPE) of polyfluorene that contains 15% fraction of 2,1,3-benzothiadiazole (BT) units (PFC3NBT) has been obtained. PFC3NBT demonstrates intramolecular energy transfer from the fluorene segments to BT sites when negatively charged species (SDS or DNAs) are added, following by a shift in emission color from blue to green, has been developed. The high density of positive charges and pendent short alkyl chains of N-propyltrimethylammoniums endow PFC3NBT with high solubility and high fluorescence quantum efficiency of 33.6% in water. The fluorescence emission properties were investigated in the presence of adverse buffer solutions, different surfactants and DNA strands. Interesting fluorescence emission quenching at short wavelength and fluorescence resonance energy transfer (FRET) induced light-on at BT sites were observed and discussed in detail. Very different from previous reports, the fluorescence emission spectra transition happens with an enhancement of integrated fluorescent intensity. The analytes induced a light-up sensing system was studied with a PFC3NBT/SDS complex mode and confirmed with DNA/DNA-FAM sensing systems. More exciting preliminary results on label-free sensing of tumor markers were also reported by investigating the unique fluorescence response to 11 kinds of proteins. These results provide a new insight view for designing CPEs with light-up and label-free features for biomolecular sensing.

Highly Contorted 1,2,5-Thiadiazole-Fused Aromatics for Solution-Processed Field-Effect Transistors: Synthesis and Properties.

A straightforward strategy has been used to construct 1,2,5-thiadiazole-fused 12-ring π systems through twofold Stille coupling and subsequent cyclodehydrogenation by utilizing the building blocks of naphthodithiophene and 5,6-substituted benzo[b]-2,1,3-thiadidazole. Molecules 1 a and 1 b, which exhibit highly contorted π surfaces, show a butterfly-shaped conformation according to DFT calculations. Within the molecules, a plane-to-plane angle of 44.8° was found. UV/Vis absorption, thermogravimetric analysis, differential scanning calorimetry, and cyclic voltammetry (CV) were used to study their physical properties. Strong intermolecular interactions of the nonplanar molecules were also observed by concentration-dependent (1) H NMR spectroscopy measurements and thin-film XRD characterization. The low-lying LUMO and high-lying HOMO levels of the molecules are -3.73 and -5.48 eV, respectively, as estimated from CV measurements; this indicates their potential as semiconducting materials for solution-processed organic field-effect transistors (OFETS). A field-effect hole mobility of up to 0.035 cm(2) V(-1) s(-1) , a threshold voltage of 6.98 V, and a current on/off ratio of 8.65×10(5) in air for 1 a have been demonstrated with the top-contact bottom-gate field-effect transistor device structures; this represents an important step toward the solution-processed OFET application of contorted aromatics.

Tumor-targeting, enzyme-activated nanoparticles for simultaneous cancer diagnosis and photodynamic therapy.

Specific targeting towards tumors and the on-site activation of photosensitizers to diagnose tumors and reduce side effects for patients are currently the main challenges for photodynamic therapy (PDT) in the clinic. Herein, uniform diiodostyryl bodipy conjugated hyaluronic acid nanoparticles (DBHA-NPs) were successfully synthesized. The evaluation of their PDT effect at both a cellular level and in animal models of tumor-bearing mice shows that the DBHA-NPs present a remarkable suppression of tumorous growth due to their specific targeting and enhanced permeability and retention (EPR) effect. More importantly, the enzyme-activated "self-assembly and disaggregation" behavior in tumors can lead to the on-site activation of DBHA-NPs, which can diagnose the tumor exactly and reduce the side effects for patients significantly. These findings confirm that DBHA-NPs have significant potential for photodynamically activated cancer theranostics in a clinical setting.

Unprecedented side reactions in Stille coupling: desired ones for Stille polycondensation.

Two types of unprecedented side reactions were identified in the Stille coupling reaction, including the direct C-H stannylation of the α-hydrogen of thiophene and the stannylation of arylbromides with trialkylstannane bromide. These results reveal the major source of enhancements for Stille polycondensation efficiency.

Conjugated Polymer Nanoparticles for Label-Free and Bioconjugate-Recognized DNA Sensing in Serum.

Hybridbio/-synthetic sensory conjugated polymer nanoparticles (CPNs) are developed for selective label-free detection of target ssDNA in serum. Carboxylic acid-functionalized anionic polyfluorene nanoparticles are rationally designed as signal amplifying unit to bioconjugate with amine functionalized single stranded oligonucleotides as a receptor. The covalent DNA coating can significantly improve the photostability of the DNA-bioconjugated CPNs over a wide range of buffer conditions. Better ssDNA discrimination for the DNA-bioconjugated CPNs sensor is achieved owing to increased interchain interactions and more efficient exciton transport in nanoparticles. The distinguishable fluorescent color for DNA-bioconjugated CPNs in the presence of target ssDNA allows naked-eye detection of ssDNA under UV irradiation.

Analysis of short-chain aliphatic amines in food and water samples using a near infrared cyanine 1-(ε-succinimydyl-hexanoate)-1'-methyl-3,3,3',3'-tetramethyl-indocarbocyanine-5,5'-disulfonate potassium with CE-LIF detection.

Precolumn derivatization of six short-chain aliphatic amines by a near-infrared dye, 1-(ε-succinimydyl-hexanoate)-1'-methyl-3,3,3',3'-tetramethyl-indocarbocyanine-5,5'- disulfonate potassium (MeCy5-OSu), followed by MEKC-CE-LIF detection has been developed as a method for the determination of aliphatic amines in environmental water and food. Optimum derivatization was operated nicely in pH 9.0 borate buffer at 20°C for 30 min. Well separated peaks were observed with a pH 9.5 BGE containing 10 mmol L⁻¹ phosphoric acid, 20 mmol L⁻¹ SDS, and 7% methanol buffered with 1.0 mol L⁻¹ NaOH. The separation procedure was rapidly achieved within 11 min and the matrix interferences could be effectively eliminated. A linear calibration graph was obtained for 5-200 nmol L⁻¹ analytes with a correlation coefficient in the range 0.9933-0.9995 for amines. This method was successfully utilized to determine aliphatic amines in lake, sewage water, and red wine with recoveries ranging from 96.4 to 105% and the RSDs ranging from 0.9 to 2.9%. Near-infrared, LIF-detector-compatible MeCy5-OSu was proved suitable for the accurate, sensitive, and rapid separation and determination of aliphatic amines in water and food samples.

Rapid analysis of phosphoamino acids from phosvitin by near-infrared cyanine 1-(ε-succinimydyl-hexanoate)-1'-methyl-3,3,3',3'-tetramethyl-indocarbocyanine-5,5'-disulfonate potassium derivatization and polyacrylamide-coated CE with LIF detection.

A polyacrylamide-coated CE method with LIF detection was developed for analyzing three phosphoamino acids including phosphotyrosine (p-Tyr), phosphothreonine (p-Thr), and phosphoserine (p-Ser). A near-infrared dye, 1-(ε-succinimydyl-hexanoate)-1'-methyl-3,3,3',3'-tetramethyl-indocarbocyanine-5,5'-disulfonate potassium (MeCy5-OSu) was employed for derivatization of these phosphoamino acids. Results indicated that the complete baseline resolution of each phosphoamino acid was obtained within 6.1 min, using 10 mmol/L phosphate buffer (pH 4.0) containing 60 mmol/L SDS as running buffer. The highest derivatization efficiency was achieved in 0.2 mol/L borate buffer (pH 8.8) for 30 min at 30 °C. Linearity of response was found in the range of 0.05-1 µmol/L. The correlation coefficients for these phosphoamino acids were from 0.9940 to 0.9976. The LODs for phosphotyrosine, phosphothreonine, and phosphoserine were about 6, 8, and 8 nmol/L, respectively. The proposed method has been successfully applied to the determination of phosphoamino acids in the hydrolysis sample of a phosphorylated phosvitin. Average recoveries for phosvitin sample were in the range of 94.0-98.0% and coefficients of variation ranged from 2.7 to 4.8%.

Solvent- and pH-induced self-assembly of cationic meta-linked poly(phenylene ethynylene): effects of helix formation on amplified fluorescence quenching and Förster resonance energy transfer.

We reported here the synthesis and characterization of a novel water-soluble, meta-linked poly(phenylene ethynylene) (m-PPE-NEt(2)Me(+)) featuring quaternized side groups. We studied the solvent-induced self-assembly of m-PPE-NEt(2)Me(+) in MeOH/H(2)O solvent mixtures by using UV-vis absorption and fluorescence spectroscopies. The results showed that the polymer folded into a helical conformation and that the extent of helical folding increased with the volume % water in the solvent. This cationic polymer also exhibited unique pH-induced helix formation, which was attributed to the partial neutralization of quaternized side groups at high pH and the meta-links in the main chain of the polymer. Studies on the fluorescence quenching of m-PPE-NEt(2)Me(+) by anthraquinone-2,6-disulfonate (AQS) and Fe(CN)(6)(4-), two small-molecule anionic quenchers with different typical structures, revealed more efficient quenching of helical conformation by AQS than by Fe(CN)(6)(4-). We proposed that the two quenchers most likely interacted with the polymer helix in two different modes; that was, AQS featuring large planar aromatic ring could intercalate within adjacent π-stacked phenylene ethynylene units in the polymer helix, whereas Fe(CN)(6)(4-) mainly bound to the periphery of polymer helix through ion-pair formation. Finally, the results of FRET from the helical polymer to the fluorescein (C*)-labeled polyanions, ssDNA-C* (ssDNA: single-stranded DNA) and dsDNA-C* (dsDNA: double-stranded DNA) also suggested two different modes of interactions. As compared with the FRET to dsDNA-C*, the FRET to ssDNA-C* was slightly more efficient, which was believed to arise from the additional binding of ssDNA-C* with the polymer via intercalation of its exposed hydrophobic bases into the π stack of adjacent phenylene ethynylene units in the polymer helix.

Quantification of polyamines in human erythrocytes using a new near-infrared cyanine 1-(epsilon-succinimidyl-hexanoate)-1'-methyl-3,3,3',3'-tetramethyl-indocarbocyanine-5,5'-disulfonate potassium with CE-LIF detection.

A novel near-infrared (NIR) cyanine 1-(epsilon-succinimidyl-hexanoate)-1'-methyl-3,3,3',3'-tetramethyl-indocarbocyanine-5,5'-disulfonate potassium (MeCy5-OSu) has been developed in our laboratory. Simultaneous determination of MeCy5-OSu-derivatized polyamines spermine (Spm), spermidine (Spd), cadaverine (Cad), and putrescine (Put) based on the separation by CE combined with diode LIF detection has been accomplished. The highest derivatization efficiency was achieved in 0.2 mol/L borate buffer (pH 8.8) for 20 min at 25 degrees C. Polyamine derivatives were separated within 14 min in the phosphate running buffer (pH 3) containing 50 mmol/L phosphoric acid, 40 mmol/L SDS, and 35% methanol v/v. Linearity of response was obtained in the range of 10-200 nmol/L. The detection limits (S/N = 3) for Spm, Spd, Cad, and Put were 0.8, 1, 3, and 2 nmol/L, respectively. The proposed method has been successfully applied to the analysis of polyamines in erythrocytes of two healthy persons and one cancer patient. Average recoveries for erythrocyte samples were 93.6-106% and coefficients of variation ranged from 1.8 to 5.4%. The analysis of polyamines in erythrocytes can be used for studying the relationship between their changes and the carcinogenesis process involved in erythrocytes.

Spectrophotometric determination of DNA using a near infrared probe 1,1'-disulfobutyl-3,3,3',3'-tetramethylindotricarbocyanine.

A direct spectrophotometric determination of DNA in solution has been developed using a near infrared probe, 1,1'-disulfobutyl-3,3,3',3'-tetramethylindotricarbocyanine (DSTCY). In pH = 7.5 Tris-HCl buffer, the reaction of DSTCY with DNA was complete within 10 min at room temperature in the presence of cetyltrimethylammonium bromide (CTAB), which leaded to a sharp increase of the absorbance at 474 nm. The concentration of DNA can be determined in such wavelength with the linear range of 0.5-8.0 microg ml(-1) and the detection limit of 45 ng ml(-1).

A fluorescence quenching method for the determination of nitrite with Rhodamine 110.

A simple and sensitive fluorescence quenching method for the determination of trace nitrite has been developed. The method is based on the reaction of Rhodamine 110 with nitrite in acidic medium to form a new compound, which has much lower fluorescence. The optimum experimental conditions were studied. The linear range was obtained at a nitrite concentration of 1.0 x 10(-8)-3.0 x 10(-7)mol l(-1) with a detection limit of 7.0 x 10(-10) mol l(-1) (S/N=3). The proposed method has been successfully applied to the determination of nitrite in tap water and lake water without extraction.