# Transformable Theranostics for imaging-guided interventions in head and neck squamous cell carcinoma

> **NIH NIH R44** · THERANOSTEC, INC. · 2021 · $480,254

## Abstract

Title: Transformable Theranostics for imaging-guided interventions in head and neck squamous cell
carcinoma
Summary/Abstract
The overall goal of this Phase II SBIR proposal is to translate our highly effective and non-toxic Transformable
Nano-Theranostics (TNTs) into clinical trials for precision image-guided intervention of head and neck squamous
cell carcinoma (HNSCC). HNSCC is the sixth most common cancer worldwide. There are around 550,000 new
cases worldwide annually and 65,630 cases in the U.S. alone. The overall survival rate of HNSCC remains
unchanged over the past 25 years. Tumor recurrence and metastasis are the leading causes of mortality.
Patients with recurrent or metastatic HNSCC have a median overall survival of only 10 months. Even with
intensive surgery, radiotherapy and chemotherapy, prognosis for these patients is still dismal. Complete surgical
removal (with negative margins) is the goal of the treatment, but can be difficult to achieve due to the infiltration
of vital structures. Since positive surgery margin is associated with poor prognosis, there is a great need to
develop novel treatments which can not only guide surgery but also destroy any residual cancer while sparing
critical organ structure and function. Moreover, development of theranostic agents that can detect and eliminate
early HNSCC lesions, particularly aggressive sub-types, could have tremendous impact in survival and function
for many patients. We recently developed a set of highly innovative TNTs that possess outstanding capability to
circumvent the sequential biological barriers which have generally hindered drug delivery to tumors, including
HNSCC. In our Phase I SBIR grant, we have optimized TNTs and demonstrated that 1) the smart dual
size/charge- transformation of TNTs in response to ubiquitous hallmarks of tumors (e.g. tumor acidosis induced
acidic extracellular pH, pHe) dramatically increased the tumor accumulation and penetration of TNTs in HNSCC
tissue, and facilitated uptake in cancer cells; 2) TNTs enabled effective visualization of tumor, drug delivery and
therapeutic effect by near infrared fluorescence imaging (NIRFI) and magnetic resonance imaging (MRI); 3) the
synergistic trimodal therapy via TNTs achieved a 100% complete cure rate in orthotopic HNSCC mouse models.
Those promising results built a solid foundation for us to move forward to the SBIR Phase II project, in which we
plan to 1) synthesize large scale Good Manufactory Production (GMP) grade TNTs, 2) perform Investigation
New Drug (IND) enabling pharmacology and toxicology studies in two species (dog and rodent), and 3) draft IND
application and design a phase I first-in-human clinical trial for HNSCC patients to determine the dose for phase
II. Our long-term goal is to develop safe, highly efficacious and cost-effective theranostic agents for human
HNSCC. The successful completion of this research will make the proposed TNTs ready for clinical trials. The
proposed transformable, tum...

## Key facts

- **NIH application ID:** 10325367
- **Project number:** 2R44CA240068-02
- **Recipient organization:** THERANOSTEC, INC.
- **Principal Investigator:** Tzu-yin Lin
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $480,254
- **Award type:** 2
- **Project period:** 2019-09-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10325367

## Citation

> US National Institutes of Health, RePORTER application 10325367, Transformable Theranostics for imaging-guided interventions in head and neck squamous cell carcinoma (2R44CA240068-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10325367. Licensed CC0.

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