Tumor-targeted hyaluronic acid-based oxidative stress nanoamplifier with ROS generation and GSH depletion for...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Tumor cells possess inherent oxidative stress, making them vulnerable to exogenous ROS.
• Overexpressed glutathione (GSH) in cancer cells scavenges ROS, limiting the effectiveness of ROS-mediated antitumor therapies.

Purpose of the Study:

• To design a tumor-targeted oxidative stress nanoamplifier to elevate intracellular ROS and suppress antioxidant systems.
• To achieve redox imbalance and effective tumor cell killing through a synergistic approach.

Main Methods:

• Synthesized cinnamaldehyde-modified hyaluronic acid (HA-CA) conjugates that self-assemble into nano-assemblies.
• Encapsulated β-phenethyl isothiocyanate (PEITC) into HA-CA nano-assemblies to form HA-CA/PEITC nanoparticles.
• Utilized the enhanced permeability and retention (EPR) effect and CD44 receptor-mediated endocytosis for tumor targeting.

Main Results:

• HA-CA/PEITC nanoparticles effectively accumulated in tumor tissues and released CA and PEITC in acidic lysosomal environments.
• The nanoparticles significantly boosted tumor cell oxidative stress by generating ROS and depleting GSH.
• Demonstrated superior antitumor efficacy in both in vitro and in vivo studies.

Conclusions:

• The developed nanoamplifier successfully augments ROS generation and suppresses GSH, leading to enhanced oxidation therapy.
• This strategy offers a promising approach for overcoming cancer cell antioxidant defenses and improving therapeutic outcomes.
• The nanoamplifier exhibits good biosafety, indicating its potential for clinical translation.