Unprecedented nanotechnological advances hold the promise to revolutionize cancer diagnostics and treatment. Nevertheless despite substantial efforts to understand cancer biology, metastases, which cause up to 90% of cancer deaths, are still poorly understood. Comprehensive studies have demonstrated the tremendous potential of using the number of circulating tumor cells (CTCs) as a marker of metastatic development. Among different CTC assays, in vivo photoacoustic (PA) flow cytometry (PAFC) demonstrates a unique capability for high-throughput, real-time study of CTCs labeled with functionalized nanoparticles (NPs) in the natural biological environment. However, despite the advantages of molecular CTC targeting, conventional labeling procedures make it difficult to track individual CTCs, which are important to understanding the mechanisms of cancer metastasis, including identification of the origin of CTCs (i.e., from primary tumor or from metastases) and the role of re-seeding or self-seeding processes. The goal of this project is to develop a platform for engineering, characterizing and optimizing nonfluorescent spectrally switchable SNPs to be used as PA contrast agents that can track individual CTCs in vivo. We hypothesize that individual CTCs targeted by NPs can be tracked through ultrafast spectral switching of NPs directly in the bloodstream using short laser pulses of specific wavelengths that are followed by real-time PA multicolor monitoring of CTCs containing the switched NPs. We will accomplish our goal test by testing this hypothesis through the following specific aims: (1) develop a platform fo engineering and characterizing spectrally switchable nanoparticles as multicolor photothermal and PA contrast agents; (2) test the capabilities of optimized switchable nanoparticles for bioconjugation and molecular targeting of cancer cells; and (3) study in vivo the properties of switchable nanoparticles and tracking of individual CTCs in the metastatic cascade via an ultrafast photoswitching. Developing this technology will allow in vivo study of CTCs that will clarify the poorly understood mechanisms of early metastatic disease and could help develop advanced diagnosis techniques and individualized therapies. Tracking individually labeled cells can improve our understanding of cell behavior in the circulatory system and provide a unique means of tracking the life cycle of any circulating cell or groups of cells. This ability can enabl the research community to discover and assess the physiological and pathological mechanisms related to health and diseases, including studies of immune system function, bacteremia, sepsis and clotting at the single cell level. The proposed technology is an advanced research tool for use in pre-clinical animal models and has the potential to be approved for human use because PA flow cytometry is safely used in humans and several NPs have been approved for pilot trials.

Public Health Relevance

Clinically relevant noninvasive, techniques for monitoring and quantifying diseases at the single-cell level in vivo have become essential tools for health care professionals in diagnosis and treatment. We propose a new nanoparticles for real-time photoacoustic tracking of circulating tumor cells leading to deadly metastasis. Taking into account the safety of photoacoustic technology for humans, we envision the development of a portable watch-like device for counting tumor cells as dynamic biomarkers of personalized therapy and signs of metastatic cancer progression, and cancer recurrence.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
Project #
Application #
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Conroy, Richard
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arkansas for Medical Sciences
Schools of Medicine
Little Rock
United States
Zip Code
Jenkins, Samir V; Nedosekin, Dmitry A; Miller, Emily K et al. (2018) Galectin-1-based tumour-targeting for gold nanostructure-mediated photothermal therapy. Int J Hyperthermia 34:19-29
Sarimollaoglu, Mustafa; Stolarz, Amanda J; Nedosekin, Dmitry A et al. (2018) High-speed microscopy for in vivo monitoring of lymph dynamics. J Biophotonics 11:e201700126
Koonce, Nathan A; Juratli, Mazen A; Cai, Chengzhong et al. (2017) Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry. Biochem Biophys Res Commun 492:507-512
Nedosekin, Dmitry A; Nolan, Jacqueline; Cai, Chengzhong et al. (2017) In vivo noninvasive analysis of graphene nanomaterial pharmacokinetics using photoacoustic flow cytometry. J Appl Toxicol 37:1297-1304
Jenkins, Samir V; Nima, Zeid A; Vang, Kieng B et al. (2017) Triple-negative breast cancer targeting and killing by EpCAM-directed, plasmonically active nanodrug systems. NPJ Precis Oncol 1:27
Galanzha, Ekaterina I; Weingold, Robert; Nedosekin, Dmitry A et al. (2017) Spaser as a biological probe. Nat Commun 8:15528
Nedosekin, Dmitry A; Fahmi, Tariq; Nima, Zeid A et al. (2017) Photoacoustic in vitro flow cytometry for nanomaterial research. Photoacoustics 6:16-25
Menyaev, Yulian A; Carey, Kai A; Nedosekin, Dmitry A et al. (2016) Preclinical photoacoustic models: application for ultrasensitive single cell malaria diagnosis in large vein and artery. Biomed Opt Express 7:3643-3658
Galanzha, Ekaterina I; Viegas, Mark G; Malinsky, Taras I et al. (2016) In vivo acoustic and photoacoustic focusing of circulating cells. Sci Rep 6:21531
Nolan, Jacqueline; Sarimollaoglu, Mustafa; Nedosekin, Dmitry A et al. (2016) In Vivo Flow Cytometry of Circulating Tumor-Associated Exosomes. Anal Cell Pathol (Amst) 2016:1628057

Showing the most recent 10 out of 17 publications