Oxidative stress is a fundamental pathological contributor to Alzheimer's disease and is closely linked to amyloid-beta-mediated toxicity, tau dysregulation, mitochondrial impairment, and progressive neuronal degeneration. Among the associated reactive oxygen species, hydrogen peroxide (H2O2) is a mechanistically relevant redox intermediate and an important oxidative stress biomarker. Herein, an Au@NH2-MIL-101(Fe) hybrid was rationally engineered as an electrocatalytically active sensing interface for H2O2 determination. The hybrid was constructed by integrating conductive Au nanodomains with an amino-functionalized Fe-based metal-organic framework, thereby combining the high surface area, porous architecture, and accessible coordination environment of NH2-MIL-101(Fe) with the superior conductivity and catalytic activity of Au. Electrochemical investigations revealed that Au@NH2-MIL-101(Fe)/SPCE exhibited substantially enhanced interfacial electron-transfer kinetics and electrocatalytic reduction of H2O2 relative to bare SPCE, MIL-101(Fe), and NH2-MIL-101(Fe). Under optimized conditions, the sensor delivered a linear range of 0.01 to 429.7 μM and a limit of detection of 0.063 µM. In addition, the platform showed good selectivity, operational stability, reproducibility, and satisfactory performance in H2O2-spiked serum and urine samples, highlighting its promise for oxidative stress-related electroanalysis relevant to Alzheimer's disease.
Clathrin-mediated endocytosis (CME) is one of the most important pathways for transporting nanoparticles (NPs) into cells. It has been demonstrated that a single large NP can effectively trigger CME when it exceeds a certain threshold, thereby carrying nearby small NPs into cells and significantly enhancing their cellular uptake. However, it is unclear what property of the NPs, mass or size, contributes more to the CME triggering. Herein, we demonstrate that size is more important than mass in CME triggering by using a special trio of accurately synthesized silica NPs. One of the trio (Ag@SNP80) with a silver core has the same size as the 80 nm silica NPs (SNP80) and the same mass as the 100 nm silica NPs (SNP100). SNP80 is smaller than the CME triggering threshold, whereas SNP100 exceeds it. By comparing the different enhancing effects of this particular trio on the cellular uptake of 40 nm silica NPs (FSNP40), we are able to compare their different capabilities in triggering CME. Results from both HeLa and A549 cells showed the same order of the enhancing effect, with SNP100 > Ag@SNP80 ≈ SNP80, clearly demonstrating that size is more important than mass in triggering CME. This conclusion is further confirmed by the enhanced cellular uptake of 70 nm polystyrene NPs (FPS70) by the trio of SNPs in the same order. This finding improves our understanding of how NPs and other materials are internalized by cells and sheds light on the fundamental mechanisms of CME.


