Dataset Information

Effective Theranostic Cyanine for Imaging of Amyloid Species in Vivo and Cognitive Improvements in Mouse Model.

ABSTRACT: We report herein an investigation of carbazole-based cyanine, (E)-4-(2-(9-(2-(2-methoxyethoxy)ethyl)-9H-carbazol-3-yl)-vinyl)-1-methyl-quinolin-1-iumiodide (SLM), as an effective theranostic agent for Alzheimer's disease (AD). This cyanine exhibited desirable multifunctional and biological properties, including amyloid-? (A?)-oligomerization inhibition, blood-brain barrier permeability, low neurotoxicity, neuroprotective effect against A?-induced toxicities, high selectivity and strong binding interactions with A? peptide/species, good biostability, as well as strong fluorescence enhancement upon binding to A? species for diagnosis and therapy of AD. This cyanine has been successfully applied to perform near-infrared in vivo imaging of A? species in transgenic AD mouse model. The triple transgenic AD mice intraperitoneally treated with SLM showed significant recovery of cognitive deficits. Furthermore, those SLM-treated mice exhibited a substantial decrease in both of oligomeric A? contents and tau proteins in their brain, which was attributed to the induction of autophagic flux. These findings demonstrated for the first time that SLM is an effective theranostic agent with in vivo efficacy for diagnosis and treatment of AD in mouse models.

SUBMITTER: Li Y

PROVIDER: S-EPMC6044748 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Effective Theranostic Cyanine for Imaging of Amyloid Species in Vivo and Cognitive Improvements in Mouse Model.

Li Yinhui Y Chen Chen C Xu Di D Poon Chung-Yan CY Ho See-Lok SL Zheng Rui R Liu Qiong Q Song Guoli G Li Hung-Wing HW Wong Man Shing MS

ACS omega 20180625 6

We report herein an investigation of carbazole-based cyanine, (<i>E</i>)-4-(2-(9-(2-(2-methoxyethoxy)ethyl)-9<i>H</i>-carbazol-3-yl)-vinyl)-1-methyl-quinolin-1-iumiodide (SLM), as an effective theranostic agent for Alzheimer's disease (AD). This cyanine exhibited desirable multifunctional and biological properties, including amyloid-β (Aβ)-oligomerization inhibition, blood-brain barrier permeability, low neurotoxicity, neuroprotective effect against Aβ-induced toxicities, high selectivity and st ...[more]

PMID: 30023962

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Project description:BackgroundAmyloid β (Aβ) is thought to initiate a cascade of pathology culminating in Alzheimer's disease-related cognitive decline. Aβ accumulation in brain tissues may begin one to two decades prior to clinical diagnosis of Alzheimer's disease. Prior studies have demonstrated that Aβ detected in vivo with positron emission tomography with amyloid ligands (amyloid-PET) predicts contemporaneously measured cognition and future cognitive trajectories. Prior studies have not evaluated the added value of Aβ measures in predicting future cognition when repeated past cognitive measures are available. We evaluated the extent to which amyloid-PET improves prediction of future cognitive changes over and above predictions based only on sociodemographics and past cognitive measures.MethodsWe used data from participants in the University of California Davis Alzheimer's Disease Research cohort who were cognitively normal at baseline, participated in amyloid-PET imaging, and completed at least three cognitive assessments prior to amyloid-PET imaging (N = 132 for memory andN = 135 for executive function). We used sociodemographic and cognitive measures taken prior to amyloid-PET imaging to predict cognitive trajectory after amyloid-PET imaging and assessed whether measures of amyloid burden improved predictions of subsequent cognitive change. Improvements in prediction were characterized as percent reduction in the mean squared error (MSE) in predicted cognition post amyloid-PET and increase in percent variance explained.ResultsThe base model using only sociodemographics and past cognitive performance explained the majority of variance in both predicted memory measures (55.6%) and executive function measures (74.5%) following amyloid-PET. Adding amyloid positivity to the model reduced the MSE for memory by 0.2%, 95% CI: (0%, 2.6%), p = 0.48 and for executive function by 3.4%, 95% CI: (0.6%, 10.2%), p = 0.002. This corresponded to an increase in the percent variance explained of 0.1%, 95% CI: (0%, 1.2%) for memory and 0.9%, 95% CI: (0.1%, 2.8%) for executive function. Similar results were obtained using a continuous measure of amyloid burden.ConclusionIn this cohort, the addition of amyloid burden slightly improved predictions of executive function compared to models based only on past cognitive assessments and sociodemographics. When repeated cognitive assessments are available, the additional utility of amyloid-PET in predicting future cognitive impairment may be limited.

Project description:Magnetic resonance (MR) nano-theranostic hyperthermia uses magnetic nanoparticles to target and accumulate at the lesions and generate heat to kill lesion cells directly through hyperthermia or indirectly through thermal activation and control releasing of drugs. Preclinical and translational applications of MR nano-theranostic hyperthermia are currently limited by a few major theoretical difficulties and experimental challenges in in vivo conditions. For example, conventional models for estimating the heat generated and the optimal magnetic nanoparticle sizes for hyperthermia do not accurately reproduce reported in vivo experimental results. In this work, a revised cluster-based model was proposed to predict the specific loss power (SLP) by explicitly considering magnetic nanoparticle aggregation in in vivo conditions. By comparing with the reported experimental results of magnetite Fe3O4 and cobalt ferrite CoFe2O4 magnetic nanoparticles, it is shown that the revised cluster-based model provides a more accurate prediction of the experimental values than the conventional models that assume magnetic nanoparticles act as single units. It also provides a clear physical picture: the aggregation of magnetic nanoparticles increases the cluster magnetic anisotropy while reducing both the cluster domain magnetization and the average magnetic moment, which, in turn, shift the predicted SLP toward a smaller magnetic nanoparticle diameter with lower peak values. As a result, the heating efficiency and the SLP values are decreased. The improvement in the prediction accuracy in in vivo conditions is particularly pronounced when the magnetic nanoparticle diameter is in the range of ~10-20 nm. This happens to be an important size range for MR cancer nano-theranostics, as it exhibits the highest efficacy against both primary and metastatic tumors in vivo. Our studies show that a relatively 20%-25% smaller magnetic nanoparticle diameter should be chosen to reach the maximal heating efficiency in comparison with the optimal size predicted by previous models.

Dataset Information

Effective Theranostic Cyanine for Imaging of Amyloid Species in Vivo and Cognitive Improvements in Mouse Model.

Publications

Effective Theranostic Cyanine for Imaging of Amyloid Species in Vivo and Cognitive Improvements in Mouse Model.

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