Dual-responsive biohybrid neutrobots for active target delivery.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Microrobots offer controllable locomotion for targeted drug delivery in challenging biological environments.
• Current cell-based microrobots face immune system clearance and premature drug leakage.
• Developing biocompatible and efficient microrobots for in vivo applications remains a significant challenge.

Purpose of the Study:

• To engineer neutrophil-based microrobots (
• neutrobots
• ) capable of active cargo delivery to malignant glioma in vivo.
• To enhance microrobot biocompatibility and drug retention using natural neutrophil and bacterial membrane components.
• To investigate the dual-responsive navigation and blood-brain barrier crossing capabilities of these novel microrobots.

Main Methods:

• Neutrophils were engineered to phagocytose drug-loaded magnetic nanogels encapsulated by *Escherichia coli* membranes.
• The resulting neutrobots demonstrated controllable intravascular movement via external magnetic fields.
• Chemotactic motion along inflammatory factor gradients facilitated brain aggregation and blood-brain barrier penetration.

Main Results:

• The *E. coli* membrane camouflage enhanced phagocytosis efficiency and prevented intracellular drug leakage.
• Neutrobots successfully aggregated in the brain and crossed the blood-brain barrier autonomously.
• Targeted drug delivery by neutrobots significantly inhibited glioma cell proliferation compared to traditional methods.

Conclusions:

• Neutrobot technology offers a promising platform for precision biomedicine by leveraging natural neutrophil functions.
• This approach overcomes limitations of current artificial microrobots, including immune evasion and targeted delivery.
• Neutrobots represent a significant advancement in developing effective in vivo drug delivery systems for challenging diseases like brain cancer.