# pH Transistor Nanoprobes for Detection of Occult Nodal Metastases

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $366,698

## Abstract

Abstract
Lymph node metastasis is the most significant predictor of survival for patients with many cancers
including breast cancer and head and neck squamous cell carcinoma (HNSCC). The gold standard
for detecting metastatic disease is lymph node dissection where all regional lymph nodes are
removed and histologically analyzed. This procedure has significant morbidity so clinicians use
indirect methods to detect involved nodes such as imaging, and sentinel node biopsy (SNB). The
long-term goal of this project is to establish tumor-activatable near infrared (NIR) nanoprobes to
delineate cancer involved nodes to allow surgical removal while preserving normal structures during
surgery without relying on indirect methods which have a significant error rate. We will capitalize on
our recent invention of pH transistor nanoprobes (PTN) to target acidic tumor pH, a ubiquitous
hallmark of cancer. PTN like an electronic transistor has a binary all or nothing response, in this case
to the tumor microenvironment fluorescently turning completely on in tumors and remaining
completely off in normal tissue. This all or nothing behavior is critical for detecting the small volume
disease in lymph nodes. We adopted the PTN design to indocyanine green (I-PTN), an FDA-approved
NIR dye with a sharp pH response (∆pHON/OFF = 0.15 pH). Using a SPY Elite® clinical camera, we
have shown the effectiveness of I-PTN nanoprobes in the visualization of various solid cancers as
well as cancer involved lymph nodes. Preliminary data show accurate identification of cancer involved
lymph nodes in vivo allowing precise surgical removal. In the proposed project, we will specifically
optimize PTN activation for detecting metastatic cancer in lymph nodes. We will test the central
hypothesis that I-PTN-guided removal of cancer involved lymph nodes improves survival and without
the need for removal of all regional nodes. To test our hypothesis, we will carry out the following
specific aims: 1) Establish a series of fine-tuned ICG-PTN nanoprobes (pH 5.4 to 7.1) with 0.15 pH
increments and determine the optimal pH for detecting HNSCC and breast cancer in nodal
metastases from orthotopic xenographs 2) Evaluate the accuracy of ICG-PTN nanoprobes in the
delineation of tumor involved nodes versus uninvolved nodes. We will harvest at risk nodes in mice
bearing tumors and determine the sensitivity and specificity of pH transistor nanoprobes for detecting
nodal metastases. 3) Identify and remove cancer involved lymph nodes and primary tumors to
investigate the long-term survival benefit of ICG-PTN-guided resection.

## Key facts

- **NIH application ID:** 10168475
- **Project number:** 5R01CA211930-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jinming Gao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $366,698
- **Award type:** 5
- **Project period:** 2017-07-12 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168475

## Citation

> US National Institutes of Health, RePORTER application 10168475, pH Transistor Nanoprobes for Detection of Occult Nodal Metastases (5R01CA211930-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10168475. Licensed CC0.

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