Brain Glucose Activated MRI Contrast Agent for Early Diagnosis of Alzheimer’s Disease

ACS Appl. Mater. Interfaces

et al. 2023

Self Cite

Oxidative stress due to Cu 2+ -triggered aggregation of β-amyloid protein (Aβ) and reactive oxygen species (ROS) overexpression in the brain is an important hallmark of early stages of Alzheimer's disease (AD) pathogenesis. The ideal modulator for improving the oxidative stress microenvironment in AD brains should take both Cu 2+ and ROS into consideration, which has been rarely reported.Here, a combined therapeutic strategy was achieved by co-encapsulating superoxide dismutase (SOD) and catalase (CAT) in imine-linked covalent organic frameworks (COFs), which were modified with peptide KLVFF (T5). The nanocomposite SC@COF-T5 exhibited an oxidative stress eradicating ability through ROS elimination and Cu 2+ chelation, combined with the inhibition of Aβ42 monomer aggregation and disaggregation of Aβ42 fibrils. In vivo experiments indicated that SC@COF-T5 with a high blood−brain barrier (BBB) penetration efficiency was effective to reduce Aβ deposition, expression of pro-inflammatory cytokines, ROS levels, and neurologic damage in AD model mice, consequently rescuing memory deficits of AD mice. This work not only confirms the feasibility and merits of the therapeutic strategy regarding multiple targets for treatment of early AD pathogenesis but also opens up a novel direction for imine-linked COFs in biomedical applications.

Section: Resultsmentioning

confidence: 99%

Imine-Linked Covalent Organic Framework Modulates Oxidative Stress in Alzheimer’s Disease

Ren

ACS Appl. Mater. Interfaces

et al. 2023

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“…FT‐IR spectroscopy was used to analyze the functional groups of the ZPG@H nanocomposites (Figure 1b); 1567 cm −1 showed the vibration absorption of the imidazole framework, 3450 cm −1 showed the vibration absorption peak of OH in water molecules, and 1549 cm −1 , the vibration absorption peak of the CC double bond on the benzene ring, 37 indicating that the ligand was completely deprotonated at this position and providing the necessary conditions for the preparation of the ZIF‐8 crystal 38 . In addition, the peak at 1648 cm −1 can only be observed in the IR spectrum of ZPG@H, and this was corresponding to the NH and CH stretching of GOx, 39 confirming the successful preparation of ZPG@H. The XRD patterns of pure ZIF‐8, PdCuAu, ZIF‐8/PdCuAu, and ZPG@H are shown in Figure 1c. In addition to the decrease in diffraction intensity, there is no obvious displacement change in the diffraction angle, so there is no evident change in the ZIF‐8 crystal, which proves that the encapsulation of PdCuAu and GOx does not destroy the crystal structure of ZIF‐8.…”

Section: Resultsmentioning

confidence: 99%

Synergistic ferroptosis‐starvation therapy for bladder cancer based on hyaluronic acid modified metal–organic frameworks

Wang

Xie

Bioengineering & Transla Med

et al. 2023

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Bladder cancer (BCa) is one of the most common malignancies of the urinary tract. Metastasis and recurrence of BCa are the leading causes of poor prognosis, and only a few patients can benefit from current first‐line treatments such as chemotherapy and immunotherapy. It is urgent to develop more effective therapeutic method with low side effects. Here, a cascade nanoreactor, ZIF‐8/PdCuAu/GOx@HA (ZPG@H), is proposed for starvation therapy and ferroptosis of BCa. The ZPG@H nanoreactor was constructed by co‐encapsulation of PdCuAu nanoparticles and glucose oxidase into zeolitic imidazolate framework‐8 (ZIF‐8) modified by hyaluronic acid. The vitro results indicated that ZPG@H enhanced intracellular reactive oxygen species levels and reduced mitochondrial depolarization in the tumor microenvironment. Therefore, the integrated advantages of starvation therapy and chemodynamic therapy endow ZPG@H with a perfect ferroptosis inducing ability. This effectiveness, combined with its excellent biocompatibility and biosafety, means that ZPG@H could make a critical contribution to the development of novel BCa treatments.

Section: Tracking Neurodegenerative Disease By Activatable Mri Nanopr...mentioning

confidence: 99%

“…Recent studies suggest brain glucose is an important biomarker of AD, which could be utilized for early AD diagnosis. Zhao’s group developed a glucose activatable MRI nanoprobe (ZGMP) for the facile MRI of AD (Figure c) . The glucose-responsive nanoprobes consisted of ZIF-8, glucose oxidase, MnO 2 nanosheet, and PEG.…”

Section: Tracking Neurodegenerative Disease By Activatable Mri Nanopr...mentioning

confidence: 99%

Nanoparticle-Based Activatable MRI Probes for Disease Imaging and Monitoring

Fan

Chemical & Biomedical Imaging

Zheng

et al. 2023

Traditional diagnosis relies on identifying anatomical abnormality, which offers a stage for various anatomical imaging techniques, such as X-ray computed tomography (CT), ultrasonic imaging, and magnetic resonance imaging (MRI). The good capacity of providing anatomical details, especially for soft tissues, popularizes the clinical use of MRI. However, as the understanding of various diseases reaches the molecular level, it is gradually accepted that molecular anomaly often precedes anatomical abnormality. Therefore, molecular imaging, which is aimed at gathering various molecular information in organisms via imaging, starts to gain momentum. Unfortunately, traditional MRI is not capable of molecular imaging. As a result, there is an urgent demand for probes that enable MRI to "see" molecules. A promising design strategy for these probes is to elicit a signal change triggered by the presence of molecular targets, i.e. activation. Benefiting from the rapid development of nanotechnology, a number of nanoparticle-based activatable MRI probes have been developed for molecular imaging. This review summarizes recent advances of activatable MRI nanoprobes for imaging pathological characteristics of cancer, inflammation, and neurodegenerative diseases, with a focus on the design strategies and applications of these probes. In addition, the prospects and challenges of activatable MRI nanoprobes are also discussed.