Injectable click-crosslinked hydrogel containing resveratrol to improve the therapeutic effect in triple negative
Gi Ru Shin1, Hee Eun Kim1, Hyeon Jin Ju1
1Department of Molecular Science and Technology, Ajou University, Suwon, 16499, South Korea.
Abstract:
Triple-negative breast cancer (TNBC) patients are considered intractable, as this disease has few effective treatments and a very poor prognosis even in its early stages. Here, intratumoral therapy with resveratrol (Res), which has anticancer and metastasis inhibitory effects, was proposed for the effective treatment of TNBC. An injectable Res-loaded click-crosslinked hyaluronic acid (Res-Cx-HA) hydrogel was designed and intratumorally injected to generate a Res-Cx-HA depot inside the tumor. The Res-Cx-HA formulation exhibited good injectability into the tumor tissue, quick depot formation inside the tumor, and the depot remained inside the injected tumor for extended periods. In vivo formed Res-Cx-HA depots sustained Res inside the tumor for extended periods. More importantly, the bioavailability and therapeutic efficacy of Res remained almost exclusively within the tumor and not in other organs. Intratumoral injection of Res-Cx-HA in animal models resulted in significant negative tumor growth rates (i.e., the tumor volume decreased over time) coupled with large apoptotic cells and limited angiogenesis in tumors. Therefore, Res-Cx-HA intratumoral injection is a promising way to treat TNBC patients with high efficacy and minimal adverse effects.
Insights
Intratumoral injection of resveratrol-loaded hydrogel effectively treats triple-negative breast cancer (TNBC) by reducing tumor growth and minimizing side effects. This novel approach offers a promising, localized therapy for TNBC patients.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Delivery Systems
Background:
- Triple-negative breast cancer (TNBC) presents significant treatment challenges due to limited therapeutic options and poor prognosis.
- Resveratrol (Res) demonstrates anticancer and anti-metastasis properties, but its clinical application is hindered by bioavailability issues.
Purpose of the Study:
- To develop an injectable resveratrol-loaded click-crosslinked hyaluronic acid (Res-Cx-HA) hydrogel for intratumoral delivery.
- To evaluate the efficacy and safety of intratumoral Res-Cx-HA injection for TNBC treatment in preclinical models.
Main Methods:
- Design and synthesis of an injectable Res-Cx-HA hydrogel.
- Intratumoral injection of Res-Cx-HA into TNBC tumor models.
- Assessment of hydrogel injectability, depot formation, drug release kinetics, and biodistribution.
- Evaluation of anti-tumor efficacy, including tumor growth inhibition, apoptosis, and angiogenesis.
Main Results:
- The Res-Cx-HA formulation showed excellent injectability and rapid in-situ depot formation within the tumor.
- Res-Cx-HA depots provided sustained release of resveratrol within the tumor, with minimal drug presence in other organs.
- Intratumoral Res-Cx-HA injection significantly inhibited tumor growth, induced apoptosis, and reduced angiogenesis in TNBC models.
Conclusions:
- Intratumoral injection of Res-Cx-HA hydrogel is a promising strategy for localized and effective TNBC treatment.
- This approach enhances resveratrol's therapeutic efficacy within the tumor while minimizing systemic toxicity.
- Res-Cx-HA offers a potential new therapeutic avenue for intractable triple-negative breast cancer.
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