Tumor Microenvironment-Responsive Dual-Enzymatic Flasklike Nanobots for Enhanced Chemotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Tumor microenvironment (TME) presents challenges for drug delivery.
• Targeted drug delivery systems are crucial for enhancing chemotherapy efficacy.
• Nanoparticle-based strategies offer potential for overcoming TME barriers.

Purpose of the Study:

• To develop a glucose oxidase/catalase-driven nanobot for targeted chemotherapy delivery.
• To investigate the TME-responsive chemotactic behavior of the nanobots.
• To evaluate the efficacy of the nanobots in enhancing tumor penetration and inhibiting tumor growth.

Main Methods:

• Fabrication of tumor cell membrane-camouflaged flasklike pentosan nanobots (GC-M@FPNbots).
• Loading nanobots with doxorubicin for chemotherapy.
• Utilizing enzymatic cascade reactions (glucose oxidase/catalase) for propulsion.
• Assessing nanobot chemotaxis along proton and hydrogen peroxide gradients.
• Evaluating tumor penetration in 3D multicellular tumor spheroids and in vivo murine models.
• Comparing tumor growth inhibition rates with conventional chemotherapy.

Main Results:

• GC-M@FPNbots demonstrated chemotactic propulsion along concentration gradients in the TME.
• Enhanced extracellular matrix penetration and deep infiltration into tumor spheroids.
• Achieved a 5.7-fold increase in tumor targeting delivery efficiency compared to passive particles.
• Exhibited an 80.8% tumor growth inhibition rate over 16 days in a murine model.
• Outperformed conventional chemotherapeutic agents in tumor growth inhibition.

Conclusions:

• Dual-enzymatic nanobots show TME-responsive directional movement, mimicking immune cell chemotaxis.
• GC-M@FPNbots significantly improve tumor drug delivery and therapeutic efficacy.
• This technology holds potential for personalized cancer therapeutic strategies.