Systemically Injectable Enzyme‐Loaded Polyion Complex Vesicles as In Vivo Nanoreactors Functioning in Tumors |
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| Authors: | Dr Yasutaka Anraku Dr Akihiro Kishimura Dr Mako Kamiya Dr Sayaka Tanaka Dr Takahiro Nomoto Dr Kazuko Toh Dr Yu Matsumoto Shigeto Fukushima Daiki Sueyoshi Prof Mitsunobu R Kano Prof Yasuteru Urano Prof Nobuhiro Nishiyama Prof Kazunori Kataoka |
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| Institution: | 1. Graduate School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo, Japan;2. Faculty of Engineering, Center for Molecular Systems (CMS), Kyushu University, Nishi-ku, Fukuoka, Japan;3. Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan;4. Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Okayama University, Kita-ku, Okayama, Japan;5. Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, Midori-ku, Yokohama, Japan;6. Division of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan;7. http://www.bmw.t.u‐tokyo.ac.jp/ |
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| 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. |
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| Keywords: | drug delivery enzymes in vivo imaging nanoreactors vesicles |
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