# Reversing epithelial-mesenchymal transition in metastatic cancer cells using engineered nanomaterials and a mild photothermal effect

> **NIH NIH R15** · SOUTH DAKOTA SCHOOL OF MINES AND TECHN'Y · 2022 · $413,479

## Abstract

Project Summary
Tumor metastasis accounts for 90% of cancer-associated mortality. Epithelial-mesenchymal transition (EMT) of
cancer cells provides the cancer cells with strong migratory-invasive abilities, and more recently, to mediate the
development of chemoresistance, which is linked to cancer stem cell-like features. There is growing evidence
suggesting that targeting EMT can be used as a therapeutic approach itself, or to enhance the efficacy of other
anticancer treatments. However, the translation of EMT targeted compounds to the clinic has been challenging
due to the lack of molecular-cellular targeting specificity and efficacy. Moreover, most of these compounds only
focus on the prevention of EMT, but not on the tumor cells that have already undergone EMT. Innovations that
are more specific, effective, and broadly applicable to eliminate EMT-type cancer cells with high metastatic
capability and enhanced drug resistance hold great potential to revolutionize the treatment of tumor metastasis.
In this project, we will develop a biomaterial-based approach to reverse the EMT of cancer cells by targeting a
transmembrane EMT inducer, CD146, using engineered black phosphorus nanosheets (BPNs) and a mild
photothermal effect. Our central hypothesis is that CD146 targeted BPNs and a mild hyperthermia will
synergistically reverse the EMT in cancer cells, and thus stop the cancer cell migration and sensitize the cancer
cells to classical chemotherapy drugs. Our preliminary studies have been able to demonstrate this approach in
reversing the EMT of breast cancer cells, leading to nearly stopped cancer cell migration. As CD146 is
overexpressed on a series of metastatic cancer cells, we will extend this approach to two other cancer types
(including prostate cancer and melanoma), and uncover its working mechanism, which will lay the foundation for
the next phase in vivo studies. Three aims have been set to test the hypothesis. Aim 1 will synthesize, optimize,
and characterize CD146 targeted BPNs, and evaluate the approach based on CD146 targeted BPNs and a mild
hyperthermia for the inhibition of cancer cell migration. Aim 2 will evaluate the efficacy of this approach in
reversing the EMT process in cancer cells and the effectiveness of this approach in sensitizing the cancer cells
to classical chemotherapeutics. Aim 3 will elucidate the molecule mechanism of how this approach reverses the
EMT process in cancer cells. The proposed research is transformative in that (i) it will offer a new perspective
for treating cancers by eliminating EMT-type cancer cells and minimizing their invasiveness and
chemoresistance; and (ii) the mechanistic knowledge generated by this work will inform the future design of
biophotonic nanomaterials to modulate cell phenotypes for in vivo cancer treatment and beyond. This research
will also strengthen undergraduate research activities in biomedical engineering at the South Dakota School of
Mines and Technology by recruiting nine ...

## Key facts

- **NIH application ID:** 10514841
- **Project number:** 1R15CA274349-01
- **Recipient organization:** SOUTH DAKOTA SCHOOL OF MINES AND TECHN'Y
- **Principal Investigator:** Steve J Smith
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $413,479
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10514841

## Citation

> US National Institutes of Health, RePORTER application 10514841, Reversing epithelial-mesenchymal transition in metastatic cancer cells using engineered nanomaterials and a mild photothermal effect (1R15CA274349-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10514841. Licensed CC0.

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