# In situ cancer cell specific synthesis of gold nanoclusters for radiosensitization of pancreatic cancer

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $425,381

## Abstract

Abstract. Pancreatic cancer is one of the most aggressive human malignancies, with a yearly incidence that
equals its mortality. Radiation therapy (RT) is an integral component of modern therapy for locally advanced
unresectable pancreatic cancers. However, its ultimate utility is severely limited by the fact that some cancer
cells are resistant to RT. This problem is further amplified by the presence of gastrointestinal mucosa immediately
adjacent to the tumor that makes dose escalation difficult and often not readily achievable. A novel approach to
enhancing the radiation dose delivered to tumors is by transiently increasing the radiation-interaction probability
of the target tissues using high atomic number (Z) nanomaterials. However, pancreatic cancer is characterized
by hypovascularity in the setting of a dense stromal component that serves as a formidable physiological barrier
to the delivery of drugs and nanoparticles. Therapeutic strategies, which can bypass the desmoplasia `fortress'
and apply therapy without significantly affecting healthy cells and tissues would address the critical issues
inherently presented by the pancreatic cancer. Here we propose to solve this delivery challenge by a paradigm
shift from delivery of pre-made high-Z nanoparticles to an atomic size gold precursors (i.e., gold ions) for tumor
radiosensitization thus achieving the ultimate reduction in size of a therapeutic agent – an atomic scale. Our
hypothesis is that small gold ions (i) will uniformly distribute throughout the tumor as their diffusion is not likely
to be impeded by the stroma, and (ii) will be reduced to gold nanoparticles (GNPs) by cancer cells that (iii) will
result in cancer cell radiosensitization to RT. This hypothesis is based on our compelling preliminary data
demonstrating efficient synthesis of GNPs from gold ions inside pancreatic cancer cells but not normal cells.
Further, the biosynthesized GNPs exhibited a high nuclear localization that is critical for efficient
radiosensitization due to a higher dose delivery to nuclei by the secondary Auger electrons. In addition, a number
of recent reports demonstrated intracellular synthesis of GNPs from chloroauric acid by mammalian cells with a
preferential nuclear localization of the nanoparticles further supporting our hypothesis. Interestingly, this
phenomenon has not been previously considered for applications in radiotherapy. We see it as a highly
innovative and exciting opportunity to greatly improve radiosensitization efficiency of cancer cells in situ. We
envision clinical implementation of our approach as an added boost to significantly increase efficacy of
stereotactic body radiotherapy in patients with a pancreatic tumor. Recent clinical data from our group and others
shows that radiation dose enhancement increases overall survival of locally advanced pancreatic cancer
patients. However, the proximity of gastrointestinal mucosa to the tumor in many instances precludes this dose
escalat...

## Key facts

- **NIH application ID:** 10039805
- **Project number:** 1R21CA252156-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Sunil Krishnan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $425,381
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039805

## Citation

> US National Institutes of Health, RePORTER application 10039805, In situ cancer cell specific synthesis of gold nanoclusters for radiosensitization of pancreatic cancer (1R21CA252156-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10039805. Licensed CC0.

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