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纺锤体监测仪:实时评估和同期治疗术后肿瘤预后的工具。

Spindle Monitor: A Tool for Real-Time Assessment and Concurrent Treatment of Postoperative Tumor Prognosis.

机构信息

College of Chemistry, Jilin Province Research Center for Engineering and Technology of Spectral Analytical Instruments, Jilin University, Qianjin Street 2699, Changchun 130012, China.

School of Pharmacy, Jilin University, Qianjin Street 2699, Changchun 130012, China.

出版信息

Anal Chem. 2023 Dec 5;95(48):17654-17661. doi: 10.1021/acs.analchem.3c03403. Epub 2023 Nov 16.

DOI:10.1021/acs.analchem.3c03403
PMID:37972234
Abstract

Cancer surgery remains a mainstay in clinical treatment. However, the efficacy of subsequent therapies largely depends on the precise evaluation of postoperative prognoses, underscoring the critical need for a comprehensive and accurate assessment of surgical outcomes. Nanoprobes targeting tumors offer a promising solution for visual prognostic assessment. In this study, we developed a "Spindle Monitor" system, designated as APPADs (Au NBPs@PDA-pep-AS1411-Dox), composed of core-shell nanoparticles. The core was made up of gold nanobipyramids (Au NBPs), coated with polydopamine (PDA), and subsequently loaded with peptide chains, AS1411, and doxorubicin (Dox). Upon deployment in the acidic tumor microenvironment (TME), APPADs released substantial amounts of Dox, initiating the apoptotic process. This triggered the activity of caspase-3, which is a crucial executor in the apoptotic pathway. Consequently, DEVD, a specific recognition site for caspase-3, was cleaved, enabling the disconnection of FITC-conjugated peptide chains and the recovery of fluorescence. Through assessing this fluorescence imaging effect, local laser irradiation could be precisely guided to the postoperative site, facilitating a synergistic combination of photothermal therapy and chemotherapy. Specifically, our "Spindle Monitor" APPADs had been validated to achieve accurate fluorescence imaging and , which demonstrated its potential value as a versatile tool for evaluating postoperative prognosis in surgical treatments, such as thyroid cancer, and assessing chemotherapy efficacy in difficult cases, like late-stage osteosarcoma. This promising tool lays a good foundation for development in visual prognosis evaluation after tumor surgery.

摘要

癌症手术仍然是临床治疗的主要手段。然而,后续治疗的疗效在很大程度上取决于术后预后的精确评估,这凸显了对手术结果进行全面准确评估的迫切需要。针对肿瘤的纳米探针为可视化预后评估提供了一个有前途的解决方案。在这项研究中,我们开发了一种“纺锤体监测器”系统,命名为 APPADs(AuNBPs@PDA-pep-AS1411-Dox),由核壳纳米粒子组成。核心由金纳米双锥体(AuNBPs)组成,表面涂有聚多巴胺(PDA),随后负载肽链、AS1411 和阿霉素(Dox)。在部署到酸性肿瘤微环境(TME)中时,APPADs 会释放大量的 Dox,启动凋亡过程。这引发了半胱天冬酶-3 的活性,半胱天冬酶-3 是凋亡途径中的关键执行者。因此,DEVD,半胱天冬酶-3 的特异性识别位点,被切割,使 FITC 缀合的肽链断开连接并恢复荧光。通过评估这种荧光成像效果,可以精确地将局部激光照射引导到术后部位,实现光热治疗和化学治疗的协同结合。具体来说,我们的“纺锤体监测器”APPADs 已经被验证可以实现准确的荧光成像,这证明了它作为一种用于评估甲状腺癌等手术后预后以及评估晚期骨肉瘤等困难病例化疗效果的多功能工具的潜在价值。这个有前途的工具为肿瘤手术后的可视化预后评估的发展奠定了良好的基础。

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