Trienzyme-in-One Nanoparticle Making Multifunctional Synergistic Nanorobot for Tumor Therapy.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Current nanoparticle drug delivery systems struggle with intratumoral penetration and cellular uptake, limiting therapeutic efficacy in cancer treatment.
• Effective tumor therapy requires overcoming these barriers to achieve deeper drug penetration and enhanced cellular internalization.

Purpose of the Study:

• To develop multifunctional nanorobots capable of autonomous movement and enhanced therapeutic effects within the tumor microenvironment.
• To improve nanoparticle penetration, cellular internalization, and overall therapeutic efficacy for tumor treatment.

Main Methods:

• Sequential integration of glucose oxidase (GOx), catalase (CAT), and urease (URE) onto biotin-modified Janus nanoparticles to create UCGPJNRs.
• Utilizing endogenous urea in the tumor microenvironment as fuel for autonomous nanorobot propulsion.
• Employing motion-enhanced endocytosis and exocytosis pathways for improved tumor cell internalization.

Main Results:

• UCGPJNRs demonstrated deep intratumoral penetration (over 0.55 mm), a 5.5-fold increase compared to previous methods.
• Achieved enhanced tumor cell internalization via motion-enhanced receptor-mediated endocytosis and ER/Golgi pathway-mediated exocytosis.
• Released NH3 for selective tumor cell toxicity and increased glucose consumption (3-fold) via accelerated GOx/CAT cascade, disrupting tumor metabolism.
• Significantly amplified in vivo tumor growth inhibition rate in tumor-bearing mice.

Conclusions:

• The developed UCGPJNRs offer a promising strategy to overcome limitations in current nanoparticle-based tumor therapy.
• Multifunctional nanorobots with synergistic bioenzyme activity can significantly enhance intratumoral penetration, cellular uptake, and therapeutic outcomes.
• This approach provides a novel platform for advancing cancer treatment through engineered nanomachines.