A research team from the Faculty of Health Sciences (FHS) of University of Macau (UM) has developed a brain imaging tool for patients with Alzheimer’s disease (AD). It is a new technology for photoacoustic (PA) imaging of Copper (II) in the brains of patients with AD. The study has been published in Angew. Chem. Int. Ed. and was highlighted by ChemistryViews.

Copper is the third most abundant trace metal in the human body and plays a vital role in the various physiological and pathological activities. Copper (II) enrichment in the brain is highly related to AD pathogenesis. Therefore, highly sensitive imaging and detection of Copper (II) in the brains of patients suffering from AD is essential to a comprehensive understanding of the pathological events that occur in the brain. However, in vivo fluorescence imaging of Copper (II) in the brain still presents an enormous challenge because of limited penetration depth, the difficulty for probes to cross the blood-brain barrier (BBB), and the fluorescence quenching resulting from the paramagnetic effect of Copper (II).

PA imaging combines optical imaging and ultrasound imaging into a hybrid modality, in which biological tissue (or probes) absorbs laser pulses and emit ultrasonic waves that are easy to detect. The current design strategy for PA probes is mainly based on extending the molecular p-conjugation to enhance the signal and shift the wavelength to near-infrared (NIR) region. Unfortunately, this in turn increases the molecular size and thus makes the probe difficult to cross BBB.

To address this challenge, the research team led by Assistant Professor Zhang Xuanjun from the FHS, developed a series of activatable photoacoustic (PA) probes with low molecular weights (<440 Da), which can specifically chelate with Copper (II) to form radicals with turn-on PA signals in the NIR region. They applied these probes for brain imaging in collaboration with Sheng Zonghai, a researcher from the Shenzhen Institute of Advanced Technology (CAS), Zhang Jingjing, a professor at the Affiliated Hospital of Guangdong Medical University, and Yuan Zhen, a professor in FHS.

In the study, the probes effectively crossed BBB and allowed the researchers to visualise, for the first time, Copper (II) in a mouse brain via the PA technique. The study has also verified that the level of Copper (II) is much higher in a brain with AD than in a normal brain. These small-molecule probes are expected to find applications in AD diagnosis, drug screening, and treatment evaluation. More information about the study can be found at https://www.chemistryviews.org/details/ezine/11175574/Sounding_Out_Alzheimers_Disease.html

澳門大學致力以科研成果推動健康,其最新研發 “小分子光聲探針"能更準確、有效為“阿茲海默症"(俗稱失智症)作藥效評估。此技術由澳大健康科學學院科團隊研發,能穿越血腦障壁,檢測腦組織裡面的二價銅離子。透過分析腦部銅離子的狀況,評估失智症藥物篩選和治療的效果。相關研究最近在國際著名刊物《Angew. Chem. Int. Ed.》刊登, 並獲學術網《ChemistryViews》亮點評論。

多項研究表明,大腦中二價銅離子的富集與“阿茲海默症"發病機制密切相關。透過光聲成像技術在腦部對二價銅離子進行成像,能為“阿茲海默症"的病理研究提供重要資訊。然而,目前光聲探針的設計是通過增加“分子的p-共軛體系",使光聲信號擴展到近紅外區,但增加“共軛體系"同時導致分子量變大,不利於探針穿越血腦障壁。有見及此,澳大健康科學學院助理教授張宣軍及其團隊研發出一系列“小分子光聲探針"(分子量小於440),能高選擇性地結合二價銅離子形成自由基,並在近紅外區顯示強的光聲信號,解決了分子量變大的憂慮。

澳大團隊與中國科學院深圳先進技術研究院研究員盛宗海、廣東醫科大學附屬醫院教授張晶晶以及澳大健康科學學院教授袁振等合作,將探針應用於活體內成像,首次實現了對患有“阿茲海默症"小鼠腦部裡的二價銅離子進行光聲成像,並發現病鼠腦部的銅離子明顯高於正常小鼠 。

此項技術突破不僅為“小分子光聲探針"設計提供了嶄新的思路,更能進一步應用到生物醫學研究、疾病診斷和分析檢測領域。同時,此技術也有助“阿茲海默症"分子層面上的研究,為“阿茲海默症"藥物篩選和治療效果的評估提供了有效的檢測工具。研究可瀏覽: https://doi.org/10.1002/anie.201904047;亮點評論:https://www.chemistryviews.org/details/ezine/11175574/Sounding_Out_Alzheimers_Disease.html


UM develops brain imaging tool for Alzheimer’s disease 澳大“光聲探針"更有效評估失智症


A group photo of the research team 團隊合照