Dr Edmond Ma Dik-lung has developed the world’s first metal-based probes for imaging dopamine receptor in living cells.


馬迪龍博士的研究發現金屬配合物類探針,可用於檢測活體細胞上的多巴胺受體,並可觀察多巴胺受體在活體細胞內的活動。

The diagram shows the use of the metal-based probe for imaging and tracking of dopamine receptors in living cancer cells.


金屬探針在活體癌細胞中觀察和追蹤多巴胺受體的工作示意圖。

Date: 14 May 2018 (Monday)

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HKBU scholar develops world-first metal-based probes for detection of dopamine receptors, a cancer biomarker

浸大學者首創金屬探針 有望早期診斷肺癌等多種癌症

A team led by Dr Edmond Ma Dik-lung, Associate Professor of the Department of Chemistry of HKBU has developed the world’s first iridium(III)-based probes for imaging dopamine receptors in living cells. The discovery has enhanced the understanding of dopamine receptors in carcinogenesis, and the findings can be potentially developed as a novel early cancer detection technology. The study was published in the inside front cover of Chemical Science, the flagship journal of the Royal Society of Chemistry.

Dopamine is an important neurotransmitter in the central nervous system of the human body and plays important roles in motivation, cognition and motor control. While dopamine receptors have long been implicated in neurodegenerative diseases, such as Parkinson’s disease, recent evidence has linked dopamine receptors also with various cancers, including lung, breast and colon cancers. Traditional detection methods for dopamine receptors include the enzyme-linked immunosorbent assay (ELISA). However, such methods suffer from high cost, incompatibility with living systems, and are not suitable for the real-time study of the biological role of dopamine receptors.

The metal-based probes developed by the team are able to selectively bind to dopamine receptors on lung cancer cells, “lighting up” the cells and making them visible to the naked eye. The probes enable the monitoring and tracking of dopamine receptors in living cells in a real-time and in a non-invasive fashion. Moreover, the experiment results demonstrated that the imaging colour intensity was correlates with the expression levels of dopamine receptors on cancer cells. These probes could therefore both help to elucidate the role of dopamine receptors in the pathogenesis of cancers and offer a potential diagnostic tool for the early screening of cancers. Importantly, the metal-based probes avoid the problems of poor photostability and photobleaching that limit conventional fluorescent imaging dyes.

The research project entitled “Cell imaging of dopamine receptor using agonist labeling iridium(III) complex” was led by Dr Edmond Ma of HKBU together with Professor Leung Chung-hang of the Institute of Chinese Medical Sciences, University of Macau. Other collaborators of the project included researchers from the School of Chinese Medicine of HKBU, the City University of Hong Kong, University of Florida, USA, and Hunan University, China.

Dr Ma said, “Early detection is crucial for improving the survival rate of hard-to-treat cancers such as lung cancer, which is associated with dopamine receptor expression. For instance, data from the American Cancer Society shows that patients with early stage non-small cell lung cancer (NSCLC) have a five-year survival rate of about 92%, but this drops to only about 36% when the cancer has progressed to an advanced stage. We therefore believe that these dopamine receptor probes show great promise for the development of molecular diagnostic tools for the early detection of cancer.”

Dr Ma added that because the probes could successfully track the internalisation process of dopamine receptors in cells, they also represent powerful tools for studying the role of dopamine receptors in the pathogenesis of cancer.

浸大化學系副教授馬迪龍博士率領的研究團隊,發現一類高靈敏的金屬「銥(Iridium)配合物類探針」,可用於檢測活體細胞上的多巴胺受體,並可觀察多巴胺受體在活體細胞內的活動。這一發現將促進人類對多巴胺受體在細胞癌變中的認知,並有望發展成新一代癌症早期診斷的技術。研究成果近期在英國皇家化學會的旗艦期刊《化學科學》上發表。

多巴胺是人體中樞神經系統中重要的神經遞質,通過它的受體發揮調節情緒、運動和認知的作用。過去,學術界普遍認為多巴胺受體主要與神經性疾病相關,例如柏金遜症;近年,這觀念逐漸改變,研究發現多巴胺受體也和肺癌、乳腺癌和結腸癌等相關。傳統測試多巴胺受體的方法一般是酶聯免疫吸附測定(ELISA)試劑盒,價格昂貴,並且只能在細胞裂解液中測試,不能即時研究多巴胺受體的生物功能。

浸大團隊開發的金屬探針與癌細胞和多巴胺受體結合時,能令細胞發光,而且光度穩定。研究人員可以即時以肉眼觀察肺癌細胞富含的多巴胺受體,並且追蹤其生物過程。經實驗證明,新探針在肺癌細胞中遇上多巴胺受體時會結合,而多巴胺受體數量愈多,結合的探針越多,光度愈強。這類新探針不但能研究多巴胺受體在癌變中的作用,而且能開發出高靈敏的即時癌症早期診斷工具。尤其該銥配合物能避免傳統的熒光蛋白、有機熒光小分子因光穩定差、在實驗中伴有光漂白現象而干擾實驗結果的缺點,是理想的多巴胺受體成像探針。

該研究項目名為「Cell imaging of dopamine receptor using agonist labeling iridium(III) complex」,由浸大馬迪龍博士主導,與合作多年的澳門大學中華醫藥研究院梁重恒教授與團隊合作完成,其他合作夥伴包括浸大中醫藥學院、香港城市大學、美國佛羅里達大學,以及內地湖南大學的團隊。

馬博士說:「早期成功診斷癌症,是降低癌症死亡率的有效方法之一,尤其對於和多巴胺受體相關的肺癌。根據美國癌症協會的資料,非小細胞性肺癌早期患者的五年存活率為92%,而晚期患者的五年存活率只有36%。因此,我們相信基於這類新探針,能開發出高靈敏的即時癌症早期診斷工具,實現患者的即時、無痛苦癌症早期檢測。」

馬博士補充說,新探針成功捕捉到多巴胺受體在活體癌細胞從細胞膜向膜內轉移這一生物現象,表明新探針也是研究多巴胺受體在癌變中作用的有效工具。