应答: 多模态成像对抗糖酵解药物治疗胰腺癌微环境的研究"
Multimodal Imaging of Pancreatic Cancer Microenvironment in Response to an Antiglycolytic Drug.
发表日期:2023 Sep 14
作者:
Elnaz Sheikh, Kirti Agrawal, Sanjit Roy, David Burk, Fabrizio Donnarumma, Young H Ko, Praveen Kumar Guttula, Nrusingh C Biswal, Hem D Shukla, Manas Ranjan Gartia
来源:
Stem Cell Research & Therapy
摘要:
脂质代谢和糖酵解在癌症的进展和转移中发挥着重要作用。使用3-溴丙酮酸(3-BP)作为抗糖酵解剂在杀死胰腺癌细胞方面显示了潜力。然而,要开发一个有效的策略来避免化学耐药性,需要探索癌症药物与复杂的肿瘤相关微环境(TAMs)之间的相互作用能力。遗憾的是,目前没有一种强大且多样化的分子成像技术可用于分析TAMs。在本研究中,我们展示了使用SERS纳米标记和抗体功能化纳米颗粒在胰腺癌的同基因小鼠模型中同时对三种蛋白质生物标志物进行了概括性概述。这允许在治疗前后获得有关生物标记和TAM变化的全面信息。我们的多模态成像技术包括表面增强拉曼光谱(SERS)、免疫组化、极化光显微镜、二次谐波产生(SHG)显微镜、荧光寿命成像显微镜(FLIM)和非靶向液相色谱和质谱(LC-MS)分析。研究显示了3-BP治疗胰腺癌的功效,并通过生物信息学分析确定了药物治疗诱导的脂质物种重构和相关通路。该文章受版权保护,版权所有。
Lipid metabolism and glycolysis play crucial roles in the progression and metastasis of cancer, and the use of 3-bromopyruvate (3-BP) as an antiglycolytic agent has shown promise in killing pancreatic cancer cells. However, developing an effective strategy to avoid chemoresistance requires the ability to probe the interaction of cancer drugs with complex tumor-associated microenvironments (TAMs). Unfortunately, no robust and multiplexed molecular imaging technology is currently available to analyze TAMs. In this study, we demonstrate the simultaneous profiling of three protein biomarkers using SERS nanotags and antibody-functionalized nanoparticles in a syngeneic mouse model of pancreatic cancer. This allows for comprehensive information about biomarkers and TAM alterations before and after treatment. Our multimodal imaging techniques include surface-enhanced Raman spectroscopy (SERS), immunohistochemistry, polarized light microscopy, second harmonic generation (SHG) microscopy, fluorescence lifetime imaging microscopy (FLIM), and untargeted liquid chromatography and mass spectrometry (LC-MS) analysis. The study reveals the efficacy of 3-BP in treating pancreatic cancer and identifies drug treatment-induced lipid species remodeling and associated pathways through bioinformatics analysis. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.