Engineered platelet cell motors for boosted cancer radiosensitization

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Cell-based drug delivery faces challenges with tumor penetration and retention.
• Mobile micro/nanomotors show enhanced delivery capabilities.
• Radiosensitization can be improved by targeted delivery of therapeutic agents.

Purpose of the Study:

• To design urease-powered platelet cell motors (PLT@Au@Urease) for targeted delivery of radiosensitizers.
• To enhance tumor targeting, cellular uptake, and radiosensitization.
• To evaluate the therapeutic efficacy of these engineered motors in vivo.

Main Methods:

• Engineered platelet cell motors by in situ synthesis and loading of gold nanoparticles (radiosensitizers) into platelets.
• Conjugated urease to platelets to create a self-propulsion system.
• Investigated the generation of thrust via urease biocatalytic reactions in a urea-containing environment.
• Assessed intracellular reactive oxygen species (ROS) levels and nuclear DNA damage.
• Conducted in vivo experiments using 4T1-bearing mice.

Main Results:

• PLT@Au@Urease motors demonstrated active locomotion and efficient tumor cell targeting.
• Self-propelled motors significantly increased intracellular ROS and exacerbated DNA damage compared to non-propelled controls (PLT@Au).
• Achieved a high sensitization enhancement rate of 1.89 for PLT@Au@Urease versus 1.08 for PLT@Au.
• In vivo studies showed significant antitumor performance when PLT@Au@Urease was combined with radiation therapy.

Conclusions:

• Urease-powered platelet cell motors offer a promising strategy for enhancing radiosensitization.
• This intelligent cell motor system improves targeted delivery of radiosensitizers to tumors.
• The findings broaden the application scope of cell motor-based drug delivery systems in cancer therapy.