A Miniaturized Platform for Multiplexed Drug Response Imaging in Live Tumors.

Simple Summary: 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...

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Publicado en:Cancers Vol. 13; no. 4; pp. 653 - 654
Autores principales: Bhagavatula, Sharath, Thompson, Devon, Ahn, Sebastian W., Upadhyaya, Kunj, Lammers, Alex, Deans, Kyle, Dominas, Christine, Ferland, Benjamin, Valvo, Veronica, Liu, Guigen, Jonas, Oliver, Lyng, Fiona M.
Formato: pictorial research tables/charts Journal Article
Publicado: MDPI 2/15/2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 2/15/2021
      vid: 13
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      pub: MDPI
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        148975818
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        10.3390/cancers13040653
        148975818
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        atl: A Miniaturized Platform for Multiplexed Drug Response Imaging in Live Tumors.
      aug:
        au:
          Bhagavatula, Sharath
          Thompson, Devon
          Ahn, Sebastian W.
          Upadhyaya, Kunj
          Lammers, Alex
          Deans, Kyle
          Dominas, Christine
          Ferland, Benjamin
          Valvo, Veronica
          Liu, Guigen
          Jonas, Oliver
          Lyng, Fiona M.
        affil: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
      sug:
        subj:
          Miniaturization
          Drug Resistance
          Diagnostic Imaging
          Dose-Response Relationship
          Neoplasms
          Human
          Antineoplastic Agents
          Chemotherapy, Cancer
          Cell Death
          Drug Evaluation, Preclinical
      ab: Simple Summary: 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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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