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Published on: April 6, 2015
Noninvasively Real-Time Monitoring In-Vivo Immune Cell and Tumor Cell Interaction by NIR-II Nanosensor
Liwen Huang1,2, Jiang Ming2, Zhihua Wang1
1Department of Hematology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, P. R. China.
Abstract:
Immunocytotherapy holds significant promise as a novel cancer treatment, but its effectiveness is often hindered by delayed responses, requiring evaluations every 2-3 weeks based on current diagnostic methods. Early assessment of immune cell-tumor cell interactions could provide more timely insights into therapeutic efficacy, enabling adjustments to treatment plans. In this study, a noninvasive nanosensor (C8R-DSNP) for real-time monitoring of in vivo immune cell activities in the second near-infrared long-wavelength (NIR-II-L) window (1500-1900 nm), which offers deep tissue transparency, is reported. The C8R-DSNP responds rapidly to caspase-8, a key apoptotic signaling molecule generated during interactions between natural killer (NK-92) cells and tumor cells. Using ratiometric NIR-II-L fluorescence imaging, dynamic in vivo observations of NK-92 cells' engagement with tumor cells in a mouse model are captured. These results demonstrate tumor cells apoptosis that happens as early as 4.5 h after NK-92 cells infusion. Additionally, in vitro urine imaging confirmed the initiation of apoptosis via cleaved fluorescent small molecules, while single-cell tracking within blood vessels and tumors further elucidated immune cell dynamics. This real-time NIR-II-L monitoring approach offers valuable insights for optimizing immunocytotherapy strategies.
Insights
This study introduces a novel nanosensor for real-time monitoring of cancer immunotherapy. The technology enables early detection of immune cell-tumor cell interactions, optimizing treatment strategies.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunology
Background:
- Immunocytotherapy shows promise but faces challenges with delayed response assessment.
- Current diagnostic methods require 2-3 week intervals for evaluating therapeutic efficacy.
- Early assessment of immune cell-tumor cell interactions is crucial for timely treatment adjustments.
Purpose of the Study:
- To develop a noninvasive nanosensor for real-time in vivo monitoring of immune cell activities during cancer immunotherapy.
- To enable early detection of therapeutic responses by tracking immune cell-tumor cell interactions.
- To utilize the second near-infrared long-wavelength (NIR-II-L) window for deep tissue imaging.
Main Methods:
- Development of a responsive nanosensor (C8R-DSNP) detecting caspase-8, a marker of apoptosis.
- Utilizing ratiometric NIR-II-L fluorescence imaging for in vivo observation.
- Employing in vitro urine imaging and single-cell tracking to analyze immune cell dynamics.
Main Results:
- Demonstrated real-time monitoring of natural killer (NK-92) cell interactions with tumor cells in a mouse model.
- Observed tumor cell apoptosis as early as 4.5 hours post-NK-92 cell infusion.
- Confirmed apoptosis initiation and elucidated immune cell dynamics through various imaging techniques.
Conclusions:
- The developed C8R-DSNP nanosensor provides rapid, real-time insights into immunocytotherapy efficacy.
- This noninvasive NIR-II-L monitoring approach facilitates early assessment of therapeutic outcomes.
- The technology offers a valuable tool for optimizing immunocytotherapy strategies and patient treatment plans.
