Targeted Delivery of Geraniol via Hyaluronic Acid-Conjugation Enhances Its Anti-Tumor Activity Against Prostate Cancer

Abstract

Background

Targeted delivery systems have been developed to improve cancer treatment by reducing side effects and enhancing drug efficacy. Geraniol, a natural product, has demonstrated promising anti-cancer effects in various cancer types, including prostate cancer, which is the most commonly diagnosed cancer in men. Hyaluronic acid (HA), a natural carrier targeting CD44-positive prostate cancer cells, can be utilized in a targeted delivery system.

Purpose

This study investigated the efficacy of a conjugate of HA and geraniol linked via a disulfide bond linker (HA-SS-Geraniol) in prostate cancer.

Materials and Methods

The cytotoxicity of HA-SS-Geraniol was evaluated on human PC-3 prostate cancer cells. Flow cytometry was used to assess its effects on mitochondrial membrane potential, apoptosis, and cell cycle arrest. Additionally, proteomic analysis was conducted to explore the underlying mechanism of action induced by HA-SS-Geraniol treatment. A subcutaneous xenograft tumor model was established in nude mice to evaluate the toxicity and efficacy of HA-SS-Geraniol in vivo.

Results

The results demonstrated that HA-SS-Geraniol exhibited potent cytotoxicity against PC-3 prostate cancer cells by inducing mitochondrial membrane potential loss and apoptosis in vitro. The proteomic analysis further supported the hypothesis that HA-SS-Geraniol induces cell death through mitochondria-mediated apoptosis, as evidenced by differential protein expression. The in vivo mouse model confirmed the safety of HA-SS-Geraniol and its ability to inhibit tumor growth.

Conclusion

HA-SS-Geraniol holds promise as a biologically safe and potentially effective therapeutic agent for prostate cancer treatment. Its targeted delivery system utilizing HA as a carrier shows potential for improving the efficacy of geraniol in cancer therapy.

Keywords:

• geraniol
• hyaluronic acid
• prostate cancer
• nanoparticle
• proteomics

Acknowledgments

This work was supported by the Wenzhou-Kean University Internal Faculty Research Support Program (IRSPG202102), International Collaborative Research Program (ICRP202201), Wenzhou-Kean University Student Partnering with Faculty Research Program, WKUSPF2023023.

Disclosure

The authors report no conflicts of interest in this work.