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

Yasutaka Anraku, Akihiro Kishimura, Mako Kamiya, Sayaka Tanaka, Takahiro Nomoto, Kazuko Toh, Yu Matsumoto, Shigeto Fukushima, Daiki Sueyoshi, Mitsunobu R. Kano, Yasuteru Urano, Nobuhiro Nishiyama, Kazunori Kataoka

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)560-565
Number of pages6
JournalAngewandte Chemie - International Edition
Volume55
Issue number2
DOIs
Publication statusPublished - Jan 11 2016

Keywords

  • drug delivery
  • enzymes
  • in vivo imaging
  • nanoreactors
  • vesicles

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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  • Cite this

    Anraku, Y., Kishimura, A., Kamiya, M., Tanaka, S., Nomoto, T., Toh, K., Matsumoto, Y., Fukushima, S., Sueyoshi, D., Kano, M. R., Urano, Y., Nishiyama, N., & Kataoka, K. (2016). Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as in Vivo Nanoreactors Functioning in Tumors. Angewandte Chemie - International Edition, 55(2), 560-565. https://doi.org/10.1002/anie.201508339