A multistage assembly/disassembly strategy for tumor-targeted CO delivery

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Therapy

Background:

• Carbon monoxide (CO) shows selective cancer cell toxicity but lacks tumor-targeting ability, limiting its therapeutic efficacy.
• Developing targeted delivery systems is crucial to enhance CO's anticancer potential and minimize side effects.

Purpose of the Study:

• To design an intelligent nanomedicine for multistage-targeted delivery and controlled release of CO.
• To improve the efficacy and safety of CO-based cancer therapy through a novel assembly/disassembly strategy.

Main Methods:

• A multistage assembly/disassembly strategy was employed to create the nanomedicine.
• Mesoporous silica nanoparticles encapsulated a mitochondria-targeted, microenvironment-responsive prodrug (FeCO-TPP) and were coated with hyaluronic acid.
• The system achieved passive tumor targeting, active cell targeting, acid-responsive prodrug release, mitochondria targeting, and ROS-responsive CO release.

Main Results:

• The nanomedicine demonstrated effective multistage targeting from tumor tissue to mitochondria.
• Controlled, step-by-step disassembly facilitated localized CO release within cancer cells.
• In vitro and in vivo studies confirmed enhanced anticancer efficacy and improved safety of the CO therapy.

Conclusions:

• The developed intelligent nanomedicine successfully overcomes the limitations of traditional CO therapy.
• The multistage assembly/disassembly approach offers a promising strategy for targeted CO delivery in cancer treatment.
• This work opens new avenues for advancing targeted carbon monoxide therapy in oncology.