# ROS Targeted Therapy for Lethal Prostate Cancer

> **NIH NIH R21** · CEDARS-SINAI MEDICAL CENTER · 2022 · $229,533

## Abstract

PROJECT SUMMARY
Prostate cancer (PC) is the second leading cause of cancer mortality in American men. Current therapeutics
only show marginal efficacy and are often associated with serious side effects and drug resistance that contribute
to patient mortality. Cancer drug resistance is one of the most challenging difficulties that needs to be addressed
with innovative mechanistic knowledge and tactical application. Reactive oxygen species (ROS), such as
superoxide anion (O2−), singlet oxygen (1O2) and hydroxyl radical (·OH), are highly active metabolic by-products,
whose homeostasis is maintained by redox regulation. High levels of ROS can cause tissue damages and even
cell death. Though small molecule reactive oxygen generating agents (ROSG) that enhance intracellular ROS
levels may thus serve as anti-tumor therapeutics, the in vivo efficacy of these compounds in cancer therapy is
severely impeded by their unfavorable pharmacokinetic properties, low bioavailability, and their poor targeting
property specifically to tumor cells. In this regard, we have discovered that certain some specified near infrared
(NIR) heptamethine carbocyanine dye (HMCD) can enter cancer cells with high selectivity via organic anion
transporting polypeptide (OATP) family of carrier proteins, which are differentially expressed in cancer cells while
the expression can be further enhanced by intra-tumoral hypoxia through upregulation of transcription factor of
the hypoxia inducible factor (HIF-1α). To improve the efficacy of ROS-mediated cancer therapy, we sought to
conjugate small molecule ROSG with cancer-specific HMCD for cancer cell targeting and delivery. This
innovative project will allow us to test the potential impact of delivering small molecule ROSG directly to cancer
cells to induce apoptosis. We hypothesize that HMCD-ROSG kills cancer cells in vitro; and will also be effective
in vivo for targeted treatment of lethal PCs. The unique mechanism of action is mediated by ROS production in
cancer cell subcellular organelles, disrupting vital biologic function to elicit apoptosis. Our preliminary results
indicated that, compared with hormonal therapy and chemotherapy, PC cells could be killed more effectively by
HMCD-ROSG. The synthesis and characterization of HMCD-ROSG conjugates will be performed and the
biological activities of these new chemical entities will be tested in vitro with drug-sensitive and drug-resistant
PC cells lines and in vivo with mouse models. We will employ NIR and bioluminescence imaging modalities as
detection tools to assess specificity of the HMCD-ROSG conjugates into tumors and to study the effectiveness
of these novel compounds as anti-cancer therapeutic and sensitizing agents for high efficacy on prevention of
PC progression and metastasis. The proposed project will be performed by a scientific collaboration between a
chemist and cancer scientist. The proposal will provide a solid foundation and new aspect to the ROS-mediated
therapy as a ...

## Key facts

- **NIH application ID:** 10322179
- **Project number:** 5R21CA256419-02
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** RUOXIANG WANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $229,533
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322179

## Citation

> US National Institutes of Health, RePORTER application 10322179, ROS Targeted Therapy for Lethal Prostate Cancer (5R21CA256419-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10322179. Licensed CC0.

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