Highly dispersive AuNCs/ChOx@ZIF-8/PEI nanocomplexes for fluorescent detection of cholesterol in human serum.

Gold nanoclusters (AuNCs) are widely used in the fluorescence detection of biomolecules in human serum due to their good fluorescence properties, low toxicity, and better biocompatibility. However, the weak fluorescence intensity of AuNCs limits the fluorescence detection of molecules within a wide concentration range. It is reported that coating AuNCs in ZIF-8 with adjustable pore size can effectively improve the fluorescence intensity of AuNCs and broaden the detection range. And the AuNCs wrapped in the gaps of ZIF-8 can prevent the fluorescence quenching caused by the aggregation of AuNCs. However, ZIF-8 has high crystallinity, poor dispersion, and easy deposition, which reduces the fluorescence stability of the detection system and affects the detection. Based on the above research, the highly hydrophilic polymer PEI was modified to the surface of ZIF-8, and a kind of nanocomposite material AuNCs/ChOx@ZIF-8/PEI was obtained by co-encapsulating AuNCs prepared with glutathione as a ligand and cholesterol oxidase (ChOx) into ZIF-8 modified with PEI. The composite material emits strong red light at 650 nm under the excitation of 395-nm light, and the system can sensitively detect cholesterol (Chol) in human serum. Compared with other materials, the PEI-modified composite has better solubility and stability, so the detection effect of Chol is better. Encapsulation of ChOx in the ZIF-8 shell can protect the enzyme and increase the local concentration of ChOx, thereby speeding up the reaction rate. Compared with free AuNCs/ChOx, the quenching rate of AuNCs/ChOx@ZIF-8/PEI system is doubled. Secondly, the addition of Fe2+ to the detection process results in higher quenching rate and detection sensitivity. The system can detect Chol in the concentration range 0.1-2.4 µM, with a detection limit of 0.073 µM. The determination is a fast and sensitive strategy. In addition, the practicability of this assay in the detection of Chol in human serum has been verified. Due to its selectivity and sensitivity, it has potential application value in clinical diagnosis.

A phase I and pharmacokinetic study of afilbercept with FOLFIRI: comparison of Chinese and Caucasian populations.

Background This study assessed the preliminary safety, pharmacokinetics (PK) and anti-tumor effects of aflibercept in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) in Chinese patients with previously-treated advanced solid malignancies. Patients and Methods This open-label single-arm Phase I study conducted at two centers in China included adult (≥18 years) patients with metastatic or unresectable solid malignancies who had received ≥1 prior treatment. Patients received aflibercept 4 mg/kg IV on Day 1 followed by FOLFIRI over Days 1 and 2 every 2 weeks, and were assessed for safety, tumor response, PK parameters and immunogenicity. Post-hoc analyses included calculation of progression-free survival (PFS) for patients with colorectal cancer (CRC). Results A total of 20 patients were enrolled. The most common Grade 3/4 adverse events included neutropenia (35%), hypertension (30%), stomatitis (20%) and proteinuria (20%), and no anti-aflibercept antibodies were detected. Six patients achieved a partial response, and in 15 patients with CRC median PFS was 5.95 months (95% CI: 5.29-8.77). Free aflibercept remained in excess of VEGF-bound aflibercept for the majority of the study treatment duration. The mean free aflibercept values for Cmax (64.8 µg/mL) AUC (291 µg.day/mL), CL (0.92 L/day) and Vss (5.9 L) were similar to those measured in Caucasian patients. The addition of aflibercept did not influence the PK of the chemotherapy agents. Conclusion For Chinese patients with pre-treated advanced solid malignancies, 4 mg/kg of aflibercept in combination with FOLFIRI was well-tolerated, demonstrated preliminary anti-tumor activity and had a PK profile consistent with that in Caucasian patients.

ZIF-67-derived Co3O4 hollow nanocage with efficient peroxidase mimicking characteristic for sensitive colorimetric biosensing of dopamine.

Co3O4 hollow nanocages (Co3O4 HNCs) were prepared by simple calcination with ZIF-67 as the precursor. Compared with ordinary nano-sized Co3O4, skeletal Co3O4 HNCs have a larger specific surface area and porosity, lead to better dispersion, which can expose more catalytic active sites, and obtain higher catalytic activity. Experiments indicate that Co3O4 HNCs are used as a catalyst to make H2O2 generate O2. At the same time, Co3O4 HNCs act as bridge to accelerate the electrons transfer from the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) to the dissolved oxygen and efficiently obtain blue oxidized TMB (oxTMB) at low concentration of H2O2. Steady-state kinetic analysis shows a lower Km and a higher Vmax value than other materials, indicating its excellent affinity and high catalytic efficiency. Based on the inhibitory effect of dopamine (DA) on TMB oxidation in the system, a sensitive, visual colorimetric biosensing method is developed. The calibration curve of DA has a good linear response at both high and low concentrations. Compared with other system, it has the unique advantage of very low detection limit, while retaining a wide detection range, and realizes the accurate detection of actual samples with different concentrations.