ROS/Enzyme Dual-Responsive Drug Delivery System for Targeted Colorectal Cancer Therapy: Synergistic Chemotherapy,...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Colorectal cancer (CRC) poses a significant mortality risk, often exacerbated by chronic inflammation and gut dysbiosis.
• Current CRC therapies face challenges with systemic toxicity and limited tumor drug accumulation.
• Targeted drug delivery systems are crucial for improving CRC treatment efficacy and reducing side effects.

Purpose of the Study:

• To develop a dual-responsive (ROS/enzyme) oral drug delivery system for precise CRC therapy.
• To create KGM-CUR/PSM microspheres for enhanced tumor-specific drug accumulation and release.
• To investigate the therapeutic potential of this system in targeting the "inflammation-microbiota-tumor" axis in CRC.

Main Methods:

• Synthesized a ROS-responsive prodrug polymer (PSM) and formed CUR/PSM micelles.
• Fabricated KGM-CUR/PSM microspheres for oral delivery and targeted colorectal cancer therapy.
• Evaluated in vitro drug release, cytotoxicity, cellular uptake, and in vivo efficacy in a mouse model, including analysis of inflammatory markers and gut microbiota.

Main Results:

• KGM-CUR/PSM microspheres demonstrated ROS/enzyme-responsive drug release.
• The system showed significant anti-CRC efficacy in vitro and in vivo, inhibiting tumor growth and improving survival in mice.
• Treatment reduced inflammatory markers, restored colon architecture, and modulated gut microbiota composition, disrupting the "inflammation-microbiota-tumor" axis.

Conclusions:

• KGM-CUR/PSM microspheres offer a promising stimuli-responsive system for CRC treatment.
• The system synergistically enhances anti-tumor efficacy by inducing apoptosis, reducing inflammation, and modulating the gut microbiota.
• This approach holds potential for future clinical applications in colorectal cancer therapy.