Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 55, Issue 2, Pages 560-565Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201508339
Keywords
drug delivery; enzymes; in vivo imaging; nanoreactors; vesicles
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan
- Core Research for Evolutional Science and Technology
- Center of Innovation (COI) Program of the Japan Science and Technology Agency (JST)
- Japan Society for the Promotion of Science (JSPS) through the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program)
- Council for Science and Technology Policy (CSTP)
- Naito Foundation of Science
- Grants-in-Aid for Scientific Research [15H05951, 26288082, 16K11226, 26670738] Funding Source: KAKEN
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The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid-and polymeric-vesicle-based nanoreactors have some practical limitations. We have succeeded in preparing enzyme-loaded polyion complex vesicles (PICsomes) through a facile protein-loading method. The preservation of enzyme activity was confirmed even after cross-linking of the PICsomes. The crosslinked beta-galactosidase-loaded PICsomes (beta-gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER-beta Gal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the beta-gal@PICsomes. Intravital confocal microscopy showed continuous production of HMDER and its distribution throughout the tumor tissues. Thus, enzyme-loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.
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