ABSTRACT
Pericyte dysfunction severely undermines cerebrovascular integrity and exacerbates neurodegeneration in Alzheimer's disease (AD). However, pericyte-targeted therapy is a yet-untapped frontier for AD. Inspired by the elevation of vascular cell adhesion molecule-1 (VCAM-1) and reactive oxygen species (ROS) levels in pericyte lesions, we fabricated a multifunctional nanoprodrug by conjugating the hybrid peptide VLC, a fusion of the VCAM-1 high-affinity peptide VHS and the neuroprotective apolipoprotein mimetic peptide COG1410, to curcumin (Cur) through phenylboronic ester bond (VLC@Cur-NPs) to alleviate complex pericyte-related pathological changes. Importantly, VLC@Cur-NPs effectively homed to pericyte lesions via VLC and released their contents upon ROS stimulation to maximize their regulatory effects. Consequently, VLC@Cur-NPs markedly increased pericyte regeneration to form a positive feedback loop and thus improved neurovascular function and ultimately alleviated memory defects in APP/PS1 transgenic mice. We present a promising therapeutic strategy for AD that can precisely modulate pericytes and has the potential to treat other cerebrovascular diseases.
Subject(s)
Alzheimer Disease , Mice, Transgenic , Pericytes , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Animals , Pericytes/drug effects , Pericytes/metabolism , Pericytes/pathology , Mice , Reactive Oxygen Species/metabolism , Curcumin/pharmacology , Curcumin/chemistry , Prodrugs/pharmacology , Prodrugs/chemistry , Nanoparticles/chemistry , Vascular Cell Adhesion Molecule-1/metabolism , Humans , Peptides/chemistry , Peptides/pharmacology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistryABSTRACT
A tea residue-based biochar, Fe-BCK0.5-VB6, was obtained by pyrolysis with KOH activation and alkalization with vitamin B6, to develop the mesopore structure and functionalized surface to improve the adsorption performance on tetracycline (TC). An increased specific surface area of 455 m2·g-1 and expanded mesopore volume of 0.138 cm3·g-1 for Fe-BCK0.5-VB6, were observed. The Avrami-fractional order kinetics and Langmuir isotherm models best fitted the experimental data, indicating the characteristics of multiple kinetic stages and monolayer of TC adsorption process. Several possible interactions, including acid-base reaction, pore filling, electrostatic interactions, π-π interactions, and hydrogen bonding forces, were participated in the attachment of TC. This novel mesoporous biochar with enhanced surface alkalinity is expected with a viable future role as an efficient adsorbent in the remedies of acidic antibiotics wastewater pollution.
