Double-responsive hyaluronic acid-based prodrugs for efficient tumour targeting

Area of Science:

• Biomaterials Science
• Drug Delivery
• Oncology

Background:

• Hyaluronic acid (HA) is a natural polymer with potential for drug delivery.
• Developing targeted therapies for prostate cancer remains a critical challenge.
• Prodrug strategies can enhance drug efficacy and reduce systemic toxicity.

Purpose of the Study:

• To develop and evaluate hyaluronic acid (HA)-based prodrugs for targeted cancer chemotherapy.
• To investigate the tumor accumulation and therapeutic efficacy of double-responsive boronated HA prodrugs.
• To assess the anti-tumor activity of a quercetin-HA prodrug in a prostate cancer xenograft model.

Main Methods:

• Synthesis of HA-based prodrugs incorporating double-responsive (acid pH or oxidation) boronates.
• Administration of HA prodrugs to SCID mice bearing human prostate tumors (LNCaP).
• Quantification of HA prodrug accumulation in tumors and organs using in vivo imaging or biodistribution studies.
• Evaluation of tumor growth inhibition and dose-dependent efficacy compared to free drugs.

Main Results:

• HA prodrugs demonstrated significant accumulation in tumors (up to 40% injected dose at 24h) with minimal accumulation in other organs.
• The liver showed negligible, even anti-inflammatory, effects from the HA prodrugs.
• A quercetin-HA prodrug significantly inhibited tumor growth in a dose-dependent manner, showing up to 4 times higher efficacy than free quercetin.

Conclusions:

• Boronated hyaluronic acid (HA) represents a highly promising platform for targeted chemotherapy delivery.
• This HA-based prodrug system exhibits excellent tumor-targeting capabilities and potent anti-cancer activity.
• The double-responsive nature of the boronates enhances the potential for effective cancer treatment with improved safety profiles.