Multivariate AND-gate substrate probes as enhanced contrast agents for fluorescence-guided surgery

Multivariate AND-gate substrate probes as enhanced contrast agents for fluorescence-guided surgery
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多元与门底物探针作为荧光引导手术的增强造影剂

DOI:
10.1101/695403
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发表时间:
--
期刊:
bioRxiv
影响因子:
--
通讯作者:
Bogyo M.
Bogyo M.
中科院分区:
--
文献类型:
--
作者:
Widen J.C;Tholen M;Yim J.J;Kerriann M. C;Rogalla S;Bogyo M.

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癌症外科治疗的最大挑战是准确定位病变并清楚地界定肿瘤和正常组织之间的边界。肿瘤所在组织的特点以及它与健康组织形成不规则边界的倾向使这一点变得混乱。为了解决这些问题,分子靶向光学造影剂已经被开发出来,以在手术期间实时确定边缘。然而,对比剂的选择性往往受到靶酶或受体在肿瘤和健康组织中的表达的限制。在这里,我们介绍了一个多变量“与门”光学成像探针的概念,它需要由多个肿瘤特异性酶顺序处理才能产生荧光信号。这导致了显著提高的特异性以及总体上增强的敏感性。这种通用的方法有可能被广泛应用于选择性地针对不同疾病组织中的酶活性的复杂模式进行检测、治疗和治疗反应监测。
The greatest challenges for surgical management of cancer are precisely locating lesions and clearly defining the margins between tumors and normal tissues. This is confounded by the characteristics of the tissue where the tumor is located as well as its propensity to form irregular boundaries with healthy tissues. To address these issues, molecularly targeted optical contrast agents have been developed to define margins in real-time during surgery,. However, selectivity of a contrast agent is often limited by expression of a target enzyme or receptor in both tumor and healthy tissues. Here we introduce a concept of multivariate ‘AND-gate’ optical imaging probes that require sequential processing by multiple tumor-specific enzymes to produce a fluorescent signal. This results in dramatically improved specificity as well as overall enhanced sensitivity. This general approach has the potential to be broadly applied to selectively target complex patterns of enzyme activities in diverse disease tissues for detection, treatment and therapy response monitoring.
用于术中神经外科指导的光学技术。
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