TY - JOUR
T1 - Systemically Injectable Enzyme-Loaded Polyion Complex Vesicles as in Vivo Nanoreactors Functioning in Tumors
AU - Anraku, Yasutaka
AU - Kishimura, Akihiro
AU - Kamiya, Mako
AU - Tanaka, Sayaka
AU - Nomoto, Takahiro
AU - Toh, Kazuko
AU - Matsumoto, Yu
AU - Fukushima, Shigeto
AU - Sueyoshi, Daiki
AU - Kano, Mitsunobu R.
AU - Urano, Yasuteru
AU - Nishiyama, Nobuhiro
AU - Kataoka, Kazunori
N1 - Funding Information:
This research was supported in part by a Grant-in-Aid for Scientific Research (No. 23685037, 25107709, and 26288082 to A.K., and 24700476 to Y.A.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, Core Research for Evolutional Science and Technology, and Center of Innovation (COI) Program of the Japan Science and Technology Agency (JST), and by the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),” initiated by the Council for Science and Technology Policy (CSTP). A.K. thanks the Naito Foundation of Science for their financial support. We thank the Research Hub for Advanced Nano Characterization at the University of Tokyo for its valuable support in the TEM measurements.
Publisher Copyright:
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2016/1/11
Y1 - 2016/1/11
N2 - 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.
AB - 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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U2 - 10.1002/anie.201508339
DO - 10.1002/anie.201508339
M3 - Article
C2 - 26629778
AN - SCOPUS:84958760894
SN - 1433-7851
VL - 55
SP - 560
EP - 565
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 2
ER -