Self-exploding tumor microenvironment-responsive nanomedicine as "ROS Bomb" ignites STING pathway for triple-negative...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Therapy

Background:

• Conventional reactive oxygen species (ROS)-mediated therapies face limitations in penetration depth and substrate availability.
• Horseradish peroxidase (HRP) can catalyze artemisinin to produce ROS, offering a potential therapeutic avenue.

Purpose of the Study:

• To design and evaluate a novel nanomedicine for enhanced antitumor immunotherapy.
• To overcome the limitations of traditional ROS-based cancer treatments.

Main Methods:

• Development of a "ROS bomb" nanomedicine using silica cross-linked micelles with ROS-cleavable thioketal bonds.
• Encapsulation of artemisinin as payload and surface immobilization of HRP as a trigger.
• In situ generation of ROS within the tumor microenvironment (TME) triggered by elevated hydrogen peroxide (H₂O₂).

Main Results:

• The nanomedicine successfully released artemisinin in the H₂O₂-rich TME, initiating an HRP-catalyzed ROS cascade.
• The induced ROS burst triggered immunogenic cell death and activated the STING pathway in dendritic cells.
• Co-delivery of SN38 enhanced immune activation, leading to effective suppression of triple-negative breast tumor growth.

Conclusions:

• The developed exogenous ROS delivery strategy overcomes conventional therapy restrictions, proving potent for treating deep-seated tumors.
• This nanomedicine approach holds significant promise for advancing antitumor immunotherapy, particularly for challenging cancers like triple-negative breast cancer.