This R01 renewal proposal aims to advance the next generation of optical nanomaterial probes for ultrasensitive detection of diseased lesions in vivo, with applications to fluorescence- guided surgery (FGS). The emerging field of FGS currently lacks the pipeline of optical contrast agents that can illuminate such deep-seated lesions to permit real-time detection and precise excision by oncosurgeons. Our previous R01 project developed the first generation of lesion-targeted optical probes based on rare-earth (RE)-doped nanocomposites that can delineate cancer lesions in vivo but are not optimal for FGS applications. They have relatively high signal attenuation and require near-infrared (NIR) light for excitation, whose shorter penetration depth limits the ability to reach and detect deeper-seated lesions. Therefore, this R01 renewal application will focus on continuing our advance by designing significantly brighter SWIR-emitting nanoprobes, while broadening the context for SWIR imaging along two important pathways: First, we aspire to develop a class of an order-of-magnitude brighter SWIR emitting nanocomposites that can be excited using SWIR light, with the hypothesis that they can be excited using deeper-penetrating IR light, which will open up applications in illuminating cancers around deeper-seated retroperitoneal nodes (Aim 1A) and precisely target these to cancer-lesions in the surgical bed (Aim 1B). Secondly, we aim to develop a live-subject SWIR imaging platform that can guide precision detection of small cancer clusters in vivo (Aim 2A) and molecularly map the surgical bed to demarcate anatomical landmarks of tumor lesions, lymph nodes and para-aortic vessel endothelium (Aim 2A). We will extend this live-subject imaging platform to guide complete excision and demonstrate superior excision outcomes relative to those guided by existing fluorophores and our first generation NIR excitable RE nanoprobes (Aim 2B). The outcomes of Aim 2 will be demonstrated using an ovarian cancer peritoneal metastasis and debulking model. The overall impact of this project will be on the design of a surveillance nanotechnology based on a new class of contrast agents that can be integrated within a short wave infrared-light imaging platform technology for fluorescence-surgery guidance.

Public Health Relevance

This project proposes to innovate a new class of fluorescent contrast agents based on rare earth nanoparticles that can target diseased lesions and when illuminated with infrared light can reveal their location deeper into tissues. The idea is to use the light surveillance to guide the detection and surgeries of challenging diseases, like ovarian cancers.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
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Atanasijevic, Tatjana
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Rutgers University
Biomedical Engineering
Biomed Engr/Col Engr/Engr Sta
United States
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Zhao, Zhenghuan; Kantamneni, Harini; He, Shuqing et al. (2018) Surface-Modified Shortwave-Infrared-Emitting Nanophotonic Reporters for Gene-Therapy Applications. ACS Biomater Sci Eng 4:2305-2363
He, Shuqing; Zhao, Xinyu; Tan, Mei Chee (2017) Synthesis of Uniform Rare Earth Doped Gd2O2S Sub-micron Sized Spheres Using Gas-Aided Sulfurization and their Optical Characteristics. RSC Adv 7:35738-35751
Kantamneni, Harini; Zevon, Margot; Donzanti, Michael J et al. (2017) Surveillance nanotechnology for multi-organ cancer metastases. Nat Biomed Eng 1:993-1003
Park, Dan M; Reed, David W; Yung, Mimi C et al. (2016) Bioadsorption of Rare Earth Elements through Cell Surface Display of Lanthanide Binding Tags. Environ Sci Technol 50:2735-42
Yu, Dechao; Ballato, John; Riman, Richard E (2016) The Temperature-Dependence of Multiphonon Relaxation of Rare-Earth Ions in Solid-State Hosts. J Phys Chem C Nanomater Interfaces 120:9958-9964
Fujita, Yoshiko; Barnes, Joni; Eslamimanesh, Ali et al. (2015) Effects of Simulated Rare Earth Recycling Wastewaters on Biological Nitrification. Environ Sci Technol 49:9460-8
Ganapathy, Vidya; Moghe, Prabhas V; Roth, Charles M (2015) Targeting tumor metastases: Drug delivery mechanisms and technologies. J Control Release 219:215-223
Higgins, Laura M; Zevon, Margot; Ganapathy, Vidya et al. (2015) Line-scanning confocal microscopy for high-resolution imaging of upconverting rare-earth-based contrast agents. J Biomed Opt 20:110506
Zevon, Margot; Ganapathy, Vidya; Kantamneni, Harini et al. (2015) CXCR-4 Targeted, Short Wave Infrared (SWIR) Emitting Nanoprobes for Enhanced Deep Tissue Imaging and Micrometastatic Cancer Lesion Detection. Small 11:6347-57
Naczynski, Dominik J; Tan, Mei Chee; Riman, Richard E et al. (2014) Rare Earth Nanoprobes for Functional Biomolecular Imaging and Theranostics. J Mater Chem B 2:2958-2973