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Cancer affects one in three people worldwide. Surgery remains the primary curative option for localized cancers, but good prognoses require complete removal of primary tumors and timely recognition of metastases. To expand surgical capabilities and enhance patient outcomes, we developed a six-channel color/near-infrared image sensor inspired by the mantis shrimp visual system that enabled near-infrared fluorescence image guidance during surgery. The mantis shrimp’s unique eye, which maximizes the number of photons contributing to and the amount of information contained in each glimpse of its surroundings, is recapitulated in our single-chip imaging system that integrates arrays of vertically stacked silicon photodetectors and pixelated spectral filters. To provide information about tumor location unavailable from a single instrument, we tuned three color channels to permit an intuitive perspective of the surgical procedure and three near-infrared channels to permit multifunctional imaging of optical probes highlighting cancerous tissue. In nude athymic mice bearing human prostate tumors, our image sensor enabled simultaneous detection of two tumor-targeted fluorophores, distinguishing diseased from healthy tissue in an estimated 92% of cases. It also permitted extraction of near-infrared structured illumination enabling the mapping of the three-dimensional topography of tumors and surgical sites to within 1.2-mm error. In the operating room, during surgical resection in 18 patients with breast cancer, our image sensor further enabled sentinel lymph node mapping using clinically approved near-infrared fluorophores. The flexibility and performance afforded by this simple and compact architecture highlights the benefits of biologically inspired sensors in image-guided surgery.
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Protease-activated indocyanine green nanoprobes for intraoperative NIR fluorescence imaging of primary tumors
Tumor-targeted fluorescent probes in the near-infrared spectrum can provide invaluable information about the location and extent of primary and metastatic tumors during intraoperative procedures to ensure no residual tumors are left in the patient's body. Even though the first fluorescence-guided surgery was performed more than 50 years ago, it is still not accepted as a standard of care in part due to the lack of efficient and non-toxic targeted probes approved by regulatory agencies around the world. Herein, we report protease-activated cationic gelatin nanoparticles encapsulating indocyanine green (ICG) for the detection of primary breast tumors in murine models with high tumor-to-background ratios. Upon intravenous administration, these nanoprobes remain optically silent due to the energy resonance transfer among the bound ICG molecules. As the nanoprobes extravasate and are exposed to the acidic tumor microenvironment, their positive surface charges increase, facilitating cellular uptake. The internalized nanoprobes are activated upon proteolytic degradation of gelatin to allow high contrast between the tumor and normal tissue. Since both gelatin and ICG are FDA-approved for intravenous administration, this activatable nanoprobe can lead to quick clinical adoption and improve the treatment of patients undergoing image-guided cancer surgery.
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- Award ID(s):
- 2030421
- PAR ID:
- 10417816
- Date Published:
- Journal Name:
- Nanoscale Advances
- Volume:
- 4
- Issue:
- 19
- ISSN:
- 2516-0230
- Page Range / eLocation ID:
- 4041 to 4050
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D2NA00276K
