# Tumor-penetrating nano-theranostics for image-guided interventions in spontaneous feline head and neck cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $602,740

## Abstract

Project Summary/Abstract
Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide. Even with
intensive surgery, radiotherapy and chemotherapy, the prognosis is still dismal. Completely removal (negative
surgical margin) with surgery is the goal of the treatment, but it is 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 could not only guide the surgery but also destroy the residual tumors while
sparing normal tissues with important functions. Moreover, development of theranostic agents that can detect
and eliminate early HNSCC lesions, particularly the aggressive sub-types, will have tremendous impact in
many patients with HNSCC. We recently developed a set of highly innovative Transformable Nano-
Theranostics (TNTs) that possess outstanding capability to circumvent the sequential biological barriers which
have generally hindered drug delivery to tumors including HNSCC. We have demonstrated that 1) the smart
dual size/charge- transformation of TNTs in response to tumor acidosis could dramatically increase the tumor
accumulation and penetration of TNTs in HNSCC tissue, and facilitate uptake in cancer cells; 2) TNTs enabled
effective visualization of tumor, drug delivery and therapeutic effect by magnetic resonance imaging (MRI) and
near infrared fluorescence imaging (NIRFI); 3) the synergistic trimodal therapy via TNTs achieved a 100%
complete cure rate in orthotopic HNSCC mouse models. These highly encouraging data suggest that such
nano-platform can be translated into early detection and elimination of HNSCC lesions, which are readily
accessible to illumination with light. The goal of this proposal is to tackle the biological barriers and
translational barriers of theranostic agents via the development of highly effective, non-toxic yet easy-to-make
targeting Transformable Nano-Theranostics (t-TNTs) for image-guided intervention using companion cats with
spontaneous HNSCC. In aim 1, a robust set of t-TNT nanoconstructs with HNSCC targeting ligand will be
developed, optimized and fully characterized. In aim 2, the biodistribution and tumor targeting properties of the
selected t-TNTs will be studied with optical imaging and MRI in orthotopic HNSCC model. The in vivo toxicity
and anti-tumor efficacy of the top t-TNTs will be evaluated in HNSCC xenograft models including PDX models.
The best t-TNT nanoconstruct selected from aim 2 will be used for image-guided treatment studies in aim 3 in
cats with spontaneous HNSCC. Successful development of such theranostic agents will significantly enhance
the delivery of imaging agents and synergistic therapies of HNSCC while the therapeutic delivery process can
be monitored at various spatial and temporal resolution scales. Results from this study will be significant not
only in advancing the development of next-generation nano-theranostics f...

## Key facts

- **NIH application ID:** 10614437
- **Project number:** 5R01DE029237-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Yuanpei Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $602,740
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10614437

## Citation

> US National Institutes of Health, RePORTER application 10614437, Tumor-penetrating nano-theranostics for image-guided interventions in spontaneous feline head and neck cancer (5R01DE029237-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10614437. Licensed CC0.

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