Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Enzyme Engineering

Background:

• Limitations exist in current lipid- and polymeric-vesicle-based nanoreactors for enzyme biomedical applications.
• Developing effective enzyme delivery systems is crucial for advanced therapies.

Purpose of the Study:

• To develop and characterize enzyme-loaded polyion complex vesicles (PICsomes) as a novel nanoreactor platform.
• To evaluate the efficacy of PICsomes for targeted enzyme delivery and prodrug activation in vivo.

Main Methods:

• Enzyme-loaded PICsomes were prepared using a facile protein-loading technique.
• Enzyme activity was assessed after cross-linking of the PICsomes.
• In vivo studies involved administering cross-linked beta-galactosidase-loaded PICsomes (β-gal@PICsomes) to tumor-bearing mice and evaluating prodrug conversion.

Main Results:

• PICsomes successfully encapsulated enzymes, preserving activity post-cross-linking.
• β-gal@PICsomes demonstrated selective accumulation in tumor tissues.
• Continuous prodrug (HMDER-βGal) conversion to a fluorescent product (HMDER) was observed at the tumor site for at least 4 days.

Conclusions:

• Enzyme-loaded PICsomes represent a versatile and effective platform for enzyme delivery.
• PICsomes facilitate targeted prodrug activation at tumor sites, showing promise for enzyme prodrug therapy.
• This approach offers a viable strategy for enhancing therapeutic outcomes in cancer treatment.