An Immunosensor Using Electroactive COF as Signal Probe for Electrochemical Detection of Carcinoembryonic Antigen

Two kinds of two-dimensional (2D) covalent-organic frameworks (COF) were used to construct a sandwich-type electrochemical immunosensor for a proof-of-concept study. Vinyl-functionalized COFTab-Dva could be linked with Ab1 by the thiol–ene “click” reaction. Electroactive COFTFPB-Thi was modified with gold nanoparticles (AuNPs) to ensure the successful connection with Ab2 through Au–S bond. Meanwhile, electroactive COFTFPB-Thi was used to as signal probe to realize both the detection of carcinoembryonic antigen (CEA) and the amplification of detection signal. In detection process of the sandwich-type electrochemical immunosensor, glassy carbon electrode (GCE) was modified with 2D COFTab-Dva first then connected with Ab1 by the thiol–ene “click” reaction, next quantitative CEA was captured, followed by specificially capturing signal probe of Ab2/AuNPs/COFTFPB-Thi where AuNPs acted as nanocarriers of Ab2 and COFTFPB-Thi served as the signal producers. As the amount of CEA was increased, the amount of signal probe captured to the electrode was also increased, and the peak signal intensity of the redox reaction of COFTFPB-Thi was enhanced accordingly. Thus, the quantitative detection of CEA could be realized according to the peak signal intensity of electroactive COFTFPB-Thi. The electrochemical immunosensor owned wide detection range of 0.11 ng/mL-80 ng/mL, low detection limit of 0.034 ng/mL and good practicability. This study opens up a new revelation for quantitative detection of CEA using electroactive COF as enhanced signal probe

H₂O₂ Ratiometric Electrochemical Sensors Based on Nanospheres Derived from Ferrocence-Modified Covalent Organic Frameworks

A uniform nanosphere derived from ferrocence-modified covalent-organic frameworks (COFETTA‑TPAL-Fc­(COOH)2) with 200 nm in diameter was prepared by dehydration condensation reaction between 4,4′,4′,4′- (ethane-1,1,2,2-tetrayl) tetraaniline and terephthalaldehyde in the presence of electroactive Fc­(COOH)2. The Fc­(COOH)2 was embedded into the layers of COFETTA‑TPAL to result in the formation of nanospheres, which increased the specific surface area of the available COFETTA‑TPAL to provide more active sites due to the increase in interlayer distance. The Fc­(COOH)2 could interact with H2O2 which might undergo self-disproportionation process to produce O2 and be reduced into H2O simultaneously, whereas the generated O2 was directly reduced into H2O by COFETTA‑TPAL. The reduction peak current of the generated O2 at −0.5 V (j–0.5 V) was gradually enhanced, whereas that of Fc­(COOH)2 around 0.45 V (j0.45 V) was decreased with continuous adding of H2O2. Thus, the COFETTA‑TPAL-Fc­(COOH)2 nanospheres were used to fabricate a “on–off” nonenzymatic H2O2 ratiometric electrochemical sensor. The proposed “on–off” ratiometric electrochemical sensor showed good performance with a wide linear range of 1.1–500 μM, high sensitivity of 0.009 μM–1, and lower detection limit of 0.33 μM. The work would offer insights for design and preparation of electroactive COF and accelerate the practical application of COF in electroanalysis

Adding Vitamin E-TPGS to the Formulation of Genexol-PM: Specially Mixed Micelles Improve Drug-Loading Ability and Cytotoxicity against Multidrug-Resistant Tumors Significantly

<div><p>Genexol-PM, produced by Samyang Company (Korea) is an excellent preparation of paclitaxel (PTX) for clinical cancer treatment. However, it cannot resolve the issue of multidrug resistance (MDR)—a significant problem in the administration of PTX to cancer patients. To increase the efficacy of Genexol-PM against MDR tumors, a mixed micelle capable of serving as a vehicle for PTX was developed, and two substances were chosen as carrier materials: 1) Polyethylene glycol–polylactic acid (PEG-PLA), the original vehicle of Genexol-PM. 2) Vitamin E-TPGS, an inhibitor of P-glycoprotein (P-gp). P-gp has been proven to be the main cause of MDR. <i>In vitro</i> evaluation indicated that the mixed micelle was an ideal PTX delivery system for the treatment of MDR tumors; the mixed micelle also showed a significantly better drug-loading coefficient than Genexol-PM.</p></div

UV intensity plot of I₂ versus logarithm of the polymer mass concentration (n = 3).

<p>UV intensity plot of I₂ versus logarithm of the polymer mass concentration (n = 3).</p

Observed and predicted values for the optimized formulation.

<p>Observed and predicted values for the optimized formulation.</p

Micelle size and size distribution of (A) PEG-PLA-PTX micelles and (B) PV-PTX (PEG-PLA/Vitamin E-TPGS-PTX) mixed micelles.

<p>Transmission electron microscope (TEM) images of (C) PEG-PLA-PTX micelles and (D) PV-PTX mixed micelles (100,000×).</p

A549 cell uptake (A) after 15 min and (B) after 1 h of culture with coumarin-6-loaded (a fluorescence probe, green) PEG-PLA micelles and (C) after 15 min and (D) after 1 h of culture with coumarin-6-loaded mixed micelles.

<p>A549 cell uptake (A) after 15 min and (B) after 1 h of culture with coumarin-6-loaded (a fluorescence probe, green) PEG-PLA micelles and (C) after 15 min and (D) after 1 h of culture with coumarin-6-loaded mixed micelles.</p

Differential scanning calorimetry (DSC) thermograms of (a) PTX, (b) blank mixed micelles, and (c) PTX-loaded mixed micelles.

<p>Differential scanning calorimetry (DSC) thermograms of (a) PTX, (b) blank mixed micelles, and (c) PTX-loaded mixed micelles.</p

(a) Viability of A549 MDR tumor cells as a function of varying concentrations of blank mixed micelles; (b) <i>in vitro</i> cytotoxicity of various formulations of PTX against A549 cells (n = 6).

<p>(a) Viability of A549 MDR tumor cells as a function of varying concentrations of blank mixed micelles; (b) <i>in vitro</i> cytotoxicity of various formulations of PTX against A549 cells (n = 6).</p

Response 3D surface in terms of desirability as suggested by the simulation for the optimization work.

<p>Response 3D surface in terms of desirability as suggested by the simulation for the optimization work.</p