# Biomedical Applications of Expanded Porphyrins: Development of Gold-Texaphyrin Conjugates

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $360,416

## Abstract

This is a year -25 renewal request that addresses a recognized challenge in medicinal inorganic chemistry,
namely moving beyond platinum in oncology. To do this, a set of texaphyrin-gold conjugates is proposed.
These systems will help overwhelm the antioxidant defense network essential to tumor growth via two
overlapping mechanisms. They will also build on progress made in recent years under this grant that has led to
very promising texaphyrin-platinum conjugates that display improved efficacy and reduced toxicity relative to
FDA-approved agents, such as oxaliplatin. However, this proposal addresses a new challenge, namely using
texaphyrins to deliver gold(I) N-heterocyclic carbene complexes to tumors. There is a strong mechanistic
rationale for doing so. We have recently shown that uniquely designed, N-hetrocyclic carbene Au(I) complexes
give rise to enhanced inhibition of antioxidant activity in cancer models as a result of thioredoxin reductase
(TrxR) inhibition. On the other hand, texaphyrins are known to increase oxidative stress through redox cycling.
This complementarity is unique and exciting. It should allow us to target the antioxidant protective
network from two different directions and do so in a tumor-selective manner. To test the promise
inherent in this hypothesis, we will pursue the following specific aims:
Aim 1. Synthesize texaphyrin-Au(I) conjugates containing both labile and non-labile linkages. Use N-
heterocyclic carbenes to control gold complexation.
Aim 2. Assess the ability of the texaphyrin-Au conjugates to affect the antioxidant network. Use MTT assays to
assess anti-proliferation activity in well-studied cancer cell lines and use flow cytometry to screen for oxidative
stress response.
Aim 3. Study texaphyrin-Au conjugate cellular uptake and compartmentalization in vitro. Use analyses of metal
content (Gd, Au) and LCMS measurements of texaphyrin concentration in cellular and organ digests to confirm
whole cell uptake and subcellular localization.
Aim 4. Begin studies of toxicity and efficacy in vivo. Use murine models to determine the tolerability and
biodistribution of the most promising texaphyrin-Au conjugates and their ability to localize to solid tumors and
inhibit tumor growth in vivo.

## Key facts

- **NIH application ID:** 9881243
- **Project number:** 5R01CA068682-28
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** BRENT L IVERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $360,416
- **Award type:** 5
- **Project period:** 1990-08-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9881243

## Citation

> US National Institutes of Health, RePORTER application 9881243, Biomedical Applications of Expanded Porphyrins: Development of Gold-Texaphyrin Conjugates (5R01CA068682-28). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9881243. Licensed CC0.

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