A Miniaturized Platform for Multiplexed Drug Response Imaging in Live Tumors
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Published on: January 5, 2024
Sharath Bhagavatula1, Devon Thompson1, Sebastian W Ahn1
1Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Abstract:
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.
Insights
A novel "lab-in-a-tumor" implantable microdevice (LIT-IMD) platform allows real-time imaging of anti-cancer drug effectiveness within live tumors. This technology eliminates the need for surgical tissue removal, enabling faster and more comprehensive drug response evaluation in cancer research.
Area of Science:
- Oncology
- Biomedical Engineering
- Drug Delivery Systems
Background:
- Conventional methods for evaluating anti-cancer agent activity in tumors often require surgical resection, limiting analysis to a single timepoint.
- Existing implantable microdevices (IMDs) can deliver drugs locally but necessitate tissue removal for response assessment.
- There is a need for in situ methods to monitor drug response dynamically within tumors without invasive procedures.
Purpose of the Study:
- To develop and validate a "lab-in-a-tumor" implantable microdevice (LIT-IMD) platform for in situ imaging of chemotherapy-induced cell death.
- To enable real-time, multi-drug response evaluation within live tumors without surgical resection.
- To provide a tool for personalized cancer treatment strategies through rapid drug screening.
Main Methods:
- The LIT-IMD platform was designed to be inserted into tumors, delivering multiple drug microdoses and a fluorescent cell-death assay to discrete locations.
- An integrated miniaturized fluorescence imaging probe within the LIT-IMD captures images of drug-exposed tissues to quantify cell death.
- The platform's performance was evaluated in murine tumor models over 8 hours, with results compared to conventional microscopy and histopathology.
Main Results:
- The LIT-IMD successfully demonstrated the ability to image multi-drug response in situ within live murine tumors.
- Drug response was evaluated over an 8-hour period, providing dynamic data on chemotherapy effectiveness.
- Results from the LIT-IMD correlated well with gold-standard methods like fluorescence microscopy and histopathology.
Conclusions:
- The LIT-IMD represents the first fully integrated platform for evaluating multiple chemotherapy responses directly within a live tumor.
- This in situ imaging approach enhances the understanding of drug activity in tumors and is applicable in settings where surgery is not feasible.
- The LIT-IMD platform holds significant potential for advancing personalized cancer therapy and drug development.
