A Miniaturized Platform for Multiplexed Drug Response Imaging in Live Tumors.
A Miniaturized Platform for Multiplexed Drug Response Imaging in Live Tumors.
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DOI：
10.3390/cancers13040653
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发表时间：
2021-02-06
期刊：
影响因子：
5.2
通讯作者：
Jonas O
中科院分区：
文献类型：
--
作者：
Bhagavatula S;Thompson D;Ahn SW;Upadhyaya K;Lammers A;Deans K;Dominas C;Ferland B;Valvo V;Liu G;Jonas O
我们开发了一种植入式微型装置，将其放置在活体肿瘤中，可以直接成像各种化疗药物诱导细胞死亡的有效性，而无需去除或处理肿瘤组织。目前，药物优化是通过在用全身剂量的化疗剂治疗患者后评估肿瘤收缩来进行的;这一次仅评估单次治疗，并且通常需要数周-数月才能为特定患者找到最佳治疗策略（如果找到的话）。相比之下，使用本文提出的技术，个性化的癌症治疗策略可以在几个小时内根据特定患者的肿瘤特征进行优化和定制，而不需要手术切除组织或延长可能无效的化疗试验。通过直接观察抗癌药物在肿瘤中的活性，有可能大大扩展我们对药物反应的理解，并开发出更个性化的癌症治疗方法。最近开发了可植入微装置（IMD），以将微剂量的化疗剂局部递送到活肿瘤的受限区域中;随后可以移除组织并进行分析以评估药物反应。该方法具有快速筛选多种药物的潜力，但需要手术切除组织，并且仅在切除组织时的单个时间点评估药物反应。在这里，我们描述了一种“肿瘤实验室”植入式微设备（LIT-IMD）平台，用于成像活肿瘤内的细胞死亡药物反应，而无需手术切除或组织处理。LIT-IMD被插入到活肿瘤中，并将多个药物微剂量递送到空间离散的位置。同时，它局部提供微剂量水平的荧光细胞死亡测定，其扩散到药物暴露的组织中并在细胞死亡部位累积。集成的小型化荧光成像探针对每个区域进行成像，以评估药物诱导的细胞死亡。我们证明了使用小鼠肿瘤模型在8小时内评估多药反应的能力，并显示了与金标准常规荧光显微镜和组织病理学的相关性。这是第一次展示一个完全集成的平台，用于评估多种化疗反应原位。这种方法可以更全面地了解活体肿瘤中的药物活性，并可以将药物反应测量的实用性扩展到手术不可行的广泛环境中。
We have developed an implantable microdevice that is placed into a live tumor, and can directly image how effective various chemotherapy drugs are at inducing cell death, without having to remove or process the tumor tissue. Currently drug optimization is performed by assessing tumor shrinkage after treating a patient with systemic doses of a chemotherapy agent; this only evaluates a single treatment at a time and typically takes weeks-months before an optimal treatment strategy is found (if found at all) for a specific patient. In contrast, using the technology presented here, a personalized cancer treatment strategy can potentially be optimized and tailored to a specific patient’s tumor characteristics within several hours, without requiring surgical tissue removal or prolonged trials of potentially ineffective chemotherapies. By observing the activity of anti-cancer agents directly in tumors, there is potential to greatly expand our understanding of drug response and develop more personalized cancer treatments. Implantable microdevices (IMD) have been recently developed to deliver microdoses of chemotherapeutic agents locally into confined regions of live tumors; the tissue can be subsequently removed and analyzed to evaluate drug response. This method has the potential to rapidly screen multiple drugs, but requires surgical tissue removal and only evaluates drug response at a single timepoint when the tissue is excised. Here, we describe a “lab-in-a-tumor” implantable microdevice (LIT-IMD) platform to image cell-death drug response within a live tumor, without requiring surgical resection or tissue processing. The LIT-IMD is inserted into a live tumor and delivers multiple drug microdoses into spatially discrete locations. In parallel, it locally delivers microdose levels of a fluorescent cell-death assay, which diffuses into drug-exposed tissues and accumulates at sites of cell death. An integrated miniaturized fluorescence imaging probe images each region to evaluate drug-induced cell death. We demonstrate ability to evaluate multi-drug response over 8 h using murine tumor models and show correlation with gold-standard conventional fluorescence microscopy and histopathology. This is the first demonstration of a fully integrated platform for evaluating multiple chemotherapy responses in situ. This approach could enable a more complete understanding of drug activity in live tumors, and could expand the utility of drug-response measurements to a wide range of settings where surgery is not feasible.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
2.5
作者：
Schaafsma, Boudewijn E.;Mieog, J. Sven D.;Hutteman, Merlijn;Van der Vorst, Joost R.;Kuppen, Peter J. K.;Lowik, Clemens W. G. M.;Frangioni, John V.;Van de Velde, Cornelis J. H.;Vahrmeijer, Alexander L.
通讯作者：
Vahrmeijer, Alexander L.
影响因子：
--
作者：
Crowley, Lisa C;Scott, Adrian P;Waterhouse, Nigel J
通讯作者：
Waterhouse, Nigel J
DOI：
10.1158/1078-0432.ccr-15-2722
发表时间：
2016-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jonas O;Oudin MJ;Kosciuk T;Whitman M;Gertler FB;Cima MJ;Flaherty KT;Langer R
通讯作者：
Langer R
影响因子：
14.8
作者：
Kim, Jun Ki;Lee, Woei Ming;Kim, Pilhan;Choi, Myunghwan;Jung, Keehoon;Kim, Seonghoon;Yun, Seok Hyun
通讯作者：
Yun, Seok Hyun