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Systemically Injectable Enzyme‐Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors
Author(s) -
Anraku Yasutaka,
Kishimura Akihiro,
Kamiya Mako,
Tanaka Sayaka,
Nomoto Takahiro,
Toh Kazuko,
Matsumoto Yu,
Fukushima Shigeto,
Sueyoshi Daiki,
Kano Mitsunobu R.,
Urano Yasuteru,
Nishiyama Nobuhiro,
Kataoka Kazunori
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201508339
Subject(s) - nanoreactor , prodrug , in vivo , enzyme , vesicle , chemistry , biophysics , enzyme assay , biochemistry , catalysis , biology , microbiology and biotechnology , membrane
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 cross‐linked β‐galactosidase‐loaded PICsomes (β‐gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER‐βGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4 days after administration of the β‐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.