An intelligent Cu/ZIF-8-based nanodrug delivery system for tumor-specific and synergistic therapy via tumor microenvironment-responsive cascade reaction.

An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).

Gas-Mediated Immunoassay for the Carcinoembryonic Antigen at Atmospheric Pressure with Smartphone Coupling with the Fluorescence Quenching Length of Perovskite Capillary.

By combining the photothermal properties of the 3,3',5,5'-tetramethylbenzidine oxidation product (TMBox) with the sensitive quenching of perovskite fluorescence by ammonia gas, a gas-mediated immunoassay at atmospheric pressure was constructed, which took the fluorescence quenching length of perovskite fluorescent capillary as the signal output. First, a CsPbBr3 perovskite with surface modification of 3-aminopropyl triethoxysilane was synthesized by thermal injection and decorated to the capillary wall by glutaraldehyde cross-linking. In the presence of H2O2 and the tumor marker carcinoembryonic antigen (CEA), TMB was oxidized to TMBox by the horseradish peroxidase (HRP)-labeled CEA antibody. The photothermal effect of TMBox at 808 nm laser irradiation increases the concentration of ammonia gas, and the prepared fluorescent capillary can respond sensitively to ammonia gas. The fluorescence quenching length can be observed by the naked eye for a semiquantitative evaluation of CEA concentration. At the same time, we developed a mobile APP for the first time to measure the fluorescence quenching length. In the range of 0-20 ng mL-1, the quenching length increased linearly with the increase in CEA concentration, and the detection limit was 0.078 ng mL-1. This method has been successfully used for the detection of CEA in human serum with a recovery of 95.8%-106.5%.

Dual-mode photothermal/chemiluminescence vertical flow assay for sensitive point-of-care detection of carcinoembryonic antigen using Cu2-xAgxS@liposome on a filter membrane.

Conventional lateral flow assays based on colorimetry and fluorescence still have shortages in sensitivity and selectivity due to the severe background interference from complex human fluid sample matrices. In this work, Cu2-xAgxS nanocrystals with high photothermal conversion efficiency and good peroxidase-like activity were synthesized and applied in the construction of a dual-mode near-infrared-photothermal/chemiluminescence (CL) vertical flow assay of carcinoembryonic antigen (CEA). These two-mode principles showed nearly zero background and the synthesized Cu2-xAgxS exhibited a high photothermal conversion efficiency of 75.23%, enabling the luminol-H2O2 CL system to have over 4 min of chemiluminescence. By combining filter membrane enrichment, Cu2-xAgxS@liposome encapsulation amplification, and nanozyme catalysis, a dual-mode photothermal/CL portable assay was constructed for sensitive and accurate detection of CEA in serum, with linear ranges of 0.02-40 and 0.001-30 ng mL-1, and detection limits of 0.0023 and 0.00029 ng mL-1, respectively. Furthermore, a smartphone application and a 3D printing device were combined for point-of-care testing. This assay can be completed within 20 min, with simple operation and no need for large instruments. It exhibited good sensitivity, selectivity, and stability, and is expected to be used in early diagnosis and prevention of relevant diseases in resource-limited areas.

Iodide-Mediated Etching of Gold Nanostar for the Multicolor Visual Detection of Hydrogen Peroxide.

A multicolor visual method for the detection of hydrogen peroxide (H2O2) was reported based on the iodide-mediated surface etching of gold nanostar (AuNS). First, AuNS was prepared by a seed-mediated method in a HEPES buffer. AuNS shows two different LSPR absorbance bands at 736 nm and 550 nm, respectively. Multicolor was generated by iodide-mediated surface etching of AuNS in the presence of H2O2. Under the optimized conditions, the absorption peak Δλ had a good linear relationship with the concentration of H2O2 with a linear range from 0.67~66.67 µmol L-1, and the detection limit is 0.44 µmol L-1. It can be used to detect residual H2O2 in tap water samples. This method offered a promising visual method for point-of-care testing of H2O2-related biomarkers.

pH-Triggered visual detection of Escherichia coli based on the co-assembly of bacitracin and thymolphthalein.

A novel probe for bacteria was simply synthesized through the solvent-induced co-assembly of bacitracin (AMP) and thymolphthalein (TP) without complicated modification. Combining with aptamer-Fe3O4, AMP/TP nanoparticles were used for the colorimetric detection of Escherichia coli with good sensitivity through the NaOH-triggered blue color and a smartphone-based App.

Bacitracin-Functionalized Dextran-MoSe2 with Peroxidase-like and Near-Infrared Photothermal Activities for Low-Temperature and Synergetic Antibacterial Applications.

Bacitracin (an antimicrobial peptide, AMP)-modified dextran-MoSe2 nanosheets (AMP/dex-MoSe2 NSs) were constructed and applied for low-temperature and synergetic antibacterial applications. The near-infrared (NIR) photothermal and peroxidase-like activities of dex-MoSe2 were combined with the bacterial membrane-binding ability of AMP through electrostatic adsorption, and a multimode antibacterial method was realized. H2O2 was converted into a hydroxyl radical (·OH) by AMP/dex-MoSe2, which exhibits a higher antibacterial activity and can avoid the toxicity of a high concentration of H2O2. Importantly, the production of ·OH and the antibacterial efficiency of AMP/dex-MoSe2 were accelerated by low-temperature heat sterilization with NIR irradiation. Owing to the AMP-guided binding and destruction effect to the bacterial membrane, AMP/dex-MoSe2 shows a better antibacterial effect on Gram-negative Escherichia coli under NIR irradiation as compared to catalytic treatment or NIR photothermal sterilization alone. Furthermore, the cytotoxicity and hemolysis of AMP/dex-MoSe2 were weak and in a relatively safe range. This multimode antibacterial strategy based on the AMP/dex-MoSe2 nanozyme will pave a way for the development of more safe and efficient antibacterial applications.