# 3D Imaging of Tumor Mechanobiology Using Nanobomb Optical Coherence Elastography

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $205,146

## Abstract

ABSTRACT. Compared to normal tissues, there are well documented and functionally important changes in
mechanical properties of neoplastic cells and tumor tissue, including tissue stiffening, loss of elasticity, and
densification. Clinically, high tumor stiffness correlates with aggressive subtypes of epithelial cancers and overall
poor prognosis. The importance of mechanical deregulation is illustrated by evidence that cancer cells increase
their metastatic potential when cultured on substrates closely resembling stiffness of tumor microenvironment.
Mechanistically, a self-reinforcing link between cancer cell and ECM remodeling likely results in increased
stiffness and progressive malignization of tumor cells. Despite a growing appreciation in the importance of
understanding mechanical signaling in tumor biology, the methods for reliable high resolution measurements of
tumor mechanical properties in 3D cell models and live tumors are severely lacking. Therefore, there is an
important need to overcome this technological limitation in order to advance our understanding of cancer
progression and therapeutic strategies to revert this process.
 Here we address this limitation by developing a new high-spatial resolution method for nanobomb-Optical
Coherence Elastography (nb-OCE). OCE is an emerging optical non-invasive biomechanical imaging method
that, in principle, can detect tissue stiffness with micrometer resolution. However, existing excitation and
detection methodologies for force measurements are limited in their ability to produce highly localized
mechanical stress that is needed for high-resolution 3D elastography mapping. To solve this limitation we
propose novel “nanobomb” contrast agents for OCE that are based on lipid-coated perfluorocarbon (PFC)
nanodroplets with embedded light absorbing dyes. Illumination of PFC “nanobombs” by a pulsed laser triggers
liquid to gas transition of PFC nanodroplets due to heating produced by light absorbing chromophores in the
PFC core. Our preliminary data showed that this liquid-gas phase transition induces highly localized mechanical
stress that can be detected by OCE with a high signal-to-noise ratio (SNR). Further, this “bursting” of PFC
nanobombs and their expansion can be effectively triggered by a femtosecond laser allowing a straightforward
combination of the proposed here nb-OCE and multi-photon microscopy (MPM). This combination will provide
an unprecedented opportunity to measure tissue elasticity with high resolution in the context of tissue
morphology and function given by MPM. Here we assembled a team of experts in nanotechnology (Sokolov),
OCE instrumentation/data analysis (Larin) and multiphoton intravital imaging/tumor biology (Friedl) to
demonstrate feasibility of this combined technology in 3D spheroid cell cultures in vitro and in window tumor
models in small animals. This MPM-nbOCE technology will enable longitudinal monitoring of evolution of tissue
elasticity landscape during both tu...

## Key facts

- **NIH application ID:** 9852546
- **Project number:** 5R21CA231561-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Konstantin V Sokolov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,146
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852546

## Citation

> US National Institutes of Health, RePORTER application 9852546, 3D Imaging of Tumor Mechanobiology Using Nanobomb Optical Coherence Elastography (5R21CA231561-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9852546. Licensed CC0.

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