Dual-Responsive Turn-On T1 Imaging-Guided Mild Photothermia for Precise Apoptotic Cancer Therapy.

Apoptosis has gained increasing attention in cancer therapy as an intrinsic signaling pathway, which leads to minimal leakage of waste products from a dying cell to neighboring normal cells. Among various stimuli to trigger apoptosis, mild hyperthermia is attractive but confronts limitations of non-specific heating and acquired resistance from elevated expression of heat shock proteins. Here, a dual-stimulation activated turn-on T1 imaging-based nanoparticulate system (DAS) is developed for mild photothermia (≈43 °C)-mediated precise apoptotic cancer therapy. In the DAS, a superparamagnetic quencher (ferroferric oxide nanoparticles, Fe3 O4 NPs) and a paramagnetic enhancer (Gd-DOTA complexes) are connected via the N6-methyladenine (m6 A)-caged, Zn2+ -dependent DNAzyme molecular device. The substrate strand of the DNAzyme contains one segment of Gd-DOTA complex-labeled sequence and another one of HSP70 antisense oligonucleotide. When the DAS is taken up by cancer cells, overexpressed fat mass and obesity-associated protein (FTO) specifically demethylates the m6 A group, thereby activating DNAzymes to cleave the substrate strand and simultaneously releasing Gd-DOTA complex-labeled oligonucleotides. The restored T1 signal from the liberated Gd-DOTA complexes lights up the tumor to guide the location and time of deploying 808 nm laser irradiation. Afterward, locally generated mild photothermia works in concert with HSP70 antisense oligonucleotides to promote apoptosis of tumor cells. This highly integrated design provides an alternative strategy for mild hyperthermia-mediated precise apoptotic cancer therapy.

Biomimetic Synthesis of Ag2 Se Quantum Dots with Enhanced Photothermal Properties and as "Gatekeepers" to Cap Mesoporous Silica Nanoparticles for Chemo-Photothermal Therapy.

Ag2 Se quantum dots (QDs) with near-infrared (NIR) fluorescence have been widely utilized in NIR fluorescence imaging in vivo because of their narrow bulk band gap and excellent biocompatibility. However, most of synthesis methods for Ag2 Se QDs are expensive and the reactants are toxic. Herein, a new protein-templated biomimetic synthesis approach is proposed for the preparation of Ag2 Se QDs by employing bovine serum albumin (BSA) as a template and dispersant. The BSA-templated Ag2 Se QDs (Ag2 Se@BSA QDs) showed NIR fluorescence with high fluorescence quantum yield (≈21.2 %), excellent biocompatibility and good dispersibility in different media. Moreover, the obtained Ag2 Se@BSA QDs exhibited remarkable photothermal conversion (≈27.8 %), which could be used in photothermal therapy. As a model application in biomedicine, the Ag2 Se@BSA QDs were used as "gatekeepers" to cap mesoporous silica nanoparticles (MSNs) by means of electrostatic interaction. By taking the advantages of NIR fluorescence and photothermal property of Ag2 Se@BSA QDs, the obtained MSN-DOX-Ag2 Se nanoparticles (MDA NPs) were employed as a nanoplatform for combined chemo-photothermal therapy. Compared with free DOX and MDA NPs without NIR laser, the laser-treated MDA NPs exhibited lower cell viability in vitro, implying that Ag2 Se@BSA QDs are highly promising photothermal agents and the MDA NPs are potential carriers for chemo-photothermal therapy.

Detection of trans-fatty acids by high performance liquid chromatography coupled with in-tube solid-phase microextraction using hydrophobic polymeric monolith.

Based on in-tube solid-phase microextraction (in-tube SPME) using a hydrophobic poly (octadecyl methacrylate-co-ethylene dimethacrylate) [poly (OMA-co-EDMA)] monolith, a simple high performance liquid chromatography (HPLC) method has been developed for detection of trans-fatty acids (TFAs) as their fatty acid methyl esters (FAMEs). The poly (OMA-co-EDMA) monolithic column with high hydrophobicity was specially prepared for simultaneous microextraction, pre-separation and purification for the analytes. The pre-separation selectivity, the extraction efficiency, and the purification effect for FAMEs were investigated respectively. Furthermore, some operation parameters have been optimized in detail with respect to satisfactory extraction efficiency of the target compounds. Under the optimized conditions, the enrichment factors for model FAMEs were ranged from 58.3 to 70.9, wide linear range (0.01-1.00mg/kg) and low detection limits (LODs) (3.0-7.1µg/kg) were achieved, respectively. In addition, recoveries of the method were in the range from 83.0 to 106.4% with low relative standard deviations (RSDs) of 3.2-4.7% (n=4) at spiking levels of 0.05, 0.25 and 0.5mg/kg, respectively. Finally, the proposed method was successfully applied for detection of TFAs in practical samples, which possesses short time-consuming, low disturbance and high detection sensitivity.

Carboxymethylchitosan covalently modified capillary column for open tubular capillary electrochromatography of basic proteins and opium alkaloids.

A novel open tubular (OT) column covalently modified with hydrophilic polysaccharide, carboxymethylchitosan (CMC) as stationary phase has been developed, and employed for the separations of basic proteins and opium alkaloids by capillary electrochromatography (CEC). With the procedures including the silanization of 3-aminopropyltrimethoxysilane (APTS) and the combination of glutaraldehyde with amino-silylated silica surface and CMC, CMC was covalently bonded on the capillary inner wall and exhibited a remarkable tolerance and chemical stability against 0.1 mol/L HCl, 0.1 mol/L NaOH or some organic solvents. By varying the pH values of running buffer, a cathodic or anodic EOF could be gained in CMC modified column. With anodic EOF mode (pH<4.3), favorable separations of basic proteins (trypsin, ribonuclease A, lysozyme and cytochrome C) were successfully achieved with high column efficiencies ranging from 97,000 to 182,000 plates/m, and the undesired adsorptions of basic proteins on the inter-wall of capillary could be avoided. Good repeatability was gained with RSD of the migration time less than 1.3% for run-to-run (n=5) and less than 3.2% for day-to-day (n=3), RSD of peak area was less than 5.6% for run-to-run (n=5) and less than 8.8% for day-to-day (n=3). With cathodic EOF mode (pH>4.3), four opium alkaloids were also baseline separated in phosphate buffer (50 mmol/L, pH 6.0) with column efficiencies ranging from 92,000 to 132,000 plates/m. CMC-bonded OT capillary column might be used as an alternative medium for the further analysis of basic proteins and alkaline analytes.

Rapid analysis of trace levels of flavins by pressurized capillary electrochromatography-laser induced fluorescence detection with sulfonated N-octadecyl methacrylate monolith.

In this paper, pressurized capillary electrochromatography (pCEC) with laser induced fluorescence detection (LIF) was demonstrated as a viable approach for the separation and determination of trace flavins in human plasma, where flavins tend to be degraded ex vivo. Using a sulfonated N-octadecyl methacrylate monolithic column in isocratic pCEC separation, symmetrical peak shapes and rapid separation could be obtained in a weakly acidic mobile phase. Baseline separation of riboflavin, flavin mononucleotide and flavin adenine dinucleotide could be achieved within 4.5 min in a mobile phase containing 60% (v/v) acetonitrile and 40% (v/v) of 20 mmol L(-1) phosphate buffer (pH 4.0), with -22 kV of applied voltage and 290 psi of supplementary pressure and 0.02 mL min(-1) of flow rate. Based on a 473 nm laser diode double pumped solid state source, flavins could be determined by LIF with the detection limit (LOD) as low as 0.5 nmol L(-1) (S/N=3). The concentration ranges were 0.005-2 micromol L(-1) for RF and FMN, and 0.02-40 micromol L(-1) for FAD. Owing to the weakly acidic condition selected in this experiment, the high fluorescence quantum yields and good stability of flavins contributed to a preferable analysis. Combined with a simple clean-up procedure, this method has been proved to be effective for the rapid and selective analysis of trace levels of flavins in human plasma without sample preconcentration.