# Rational translation of gold nanoparticle mediated radiosensitization to the clinic

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $147,082

## Abstract

The use of high atomic number (Z) elements as radiosensitizers of tumors has been well documented in the
literature over the last few decades. In particular, gold nanoparticles (GNPs), typically defined as high-Z gold
structures with the longest dimension smaller than 100 nm, have been the subject of active investigation for the
same purpose for the past 15 years. Early in vivo demonstration of GNP-mediated radiosensitization (GMR)
effect was based on passive accumulation of GNPs within tumors (“passive targeting”). While resulting in a
remarkable level of GMR, this approach generally requires clinically less relevant radiation quality (low energy
kilovoltage x-rays) and clinically unachievable (without direct injection) gold concentration (up to 7mg gold per
gram of tumor). To overcome these difficulties, we have been investigating an alternative approach based on
“active targeting” which shows a promising outlook for clinical translation in the near term. This proposal seeks
to surmount the remaining challenges associated with our active targeting-based approach before embarking
on clinical translation of GMR. Specifically, we aim to identify the molecular mechanism of GMR, biodistribution
and kinetics of GNPs developed for clinical translation, their fate at the tumor and cellular levels, and the
correlation between GNP-mediated dose enhancement and GMR. Despite abundant data and publications on
GMR accumulated over the years, critical knowledge gaps still exist in terms of the aforementioned aspects,
hindering clinical translation of GMR. As demonstrated in our preliminary data, we propose to address such
issues that hold the key for clinical translation of GMR, through concerted multidisciplinary efforts. Upon
achieving this goal, a pilot human trial of GNP-enhanced radiation therapy (RT) will also be conducted within
this project for the management of recurrent rectal cancer. Overall, we will pursue three Specific Aims shown
below to achieve the goals of this project. (1) To determine the molecular mechanism of GMR, the
biodistribution/kinetics of GNPs in vitro and in vivo, and the radiosensitization efficacy in clinically relevant
treatment scenarios, (2) To correlate GNP-mediated dose enhancement and GMR using high resolution
image-based cell/tissue models and nanoscale computational techniques, and (3) To conduct a pilot human
trial of GNP-enhanced RT for previously radiated recurrent rectal cancers. Ultimately, this project would lay the
foundation for widespread applications of the currently envisioned RT paradigm that enables more potent and
tumor-specific RT with less toxicity.

## Key facts

- **NIH application ID:** 10769899
- **Project number:** 5R01CA257241-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Sang Hyun Cho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $147,082
- **Award type:** 5
- **Project period:** 2021-01-13 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769899

## Citation

> US National Institutes of Health, RePORTER application 10769899, Rational translation of gold nanoparticle mediated radiosensitization to the clinic (5R01CA257241-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10769899. Licensed CC0.

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