title: Anticancer efficacy of a supramolecular complex of a 2-diethylaminoethyl-dextran-MMA graft copolymer and paclitaxel used as an artificial enzyme.
abstract: The anticancer efficacy of a supramolecular complex that was used as an artificial enzyme against multi-drug-resistant cancer cells was confirmed. A complex of diethylaminoethyl-dextran-methacrylic acid methylester copolymer (DDMC)/paclitaxel (PTX), obtained with PTX as the guest and DDMC as the host, formed a nanoparticle 50-300 nm in size. This complex is considered to be useful as a drug delivery system (DDS) for anticancer compounds since it formed a stable polymeric micelle in water. The resistance of B16F10 melanoma cells to PTX was shown clearly through a maximum survival curve. Conversely, the DDMC/PTX complex showed a superior anticancer efficacy and cell killing rate, as determined through a Michaelis-Menten-type equation, which may promote an allosteric supramolecular reaction to tubulin, in the same manner as an enzymatic reaction. The DDMC/PTX complex showed significantly higher anticancer activity compared to PTX alone in mouse skin in vivo. The median survival times of the saline, PTX, DDMC/PTX4 (particle size 50 nm), and DDMC/PTX5 (particle size 290 nm) groups were 120 h (treatment (T)/control (C), 1.0), 176 h (T/C, 1.46), 328 h (T/C, 2.73), and 280 h (T/C, 2.33), respectively. The supramolecular DDMC/PTX complex showed twice the effectiveness of PTX alone (p < 0.036). Above all, the DDMC/PTX complex is not degraded in cells and acts as an intact supramolecular assembly, which adds a new species to the range of DDS.
authors.affiliation: Ryujyu Science Corporation, 39-4 Kosora-cho, Seto, Aichi 489-0842, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Onishi
authors.affiliation: Department of Infectious Disease Control, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Eshita
authors.affiliation: Department of Human Anatomy, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Rui-Cheng
authors.initials: RC
authors.lastname: Ji
authors.affiliation: Ryujyu Science Corporation, 39-4 Kosora-cho, Seto, Aichi 489-0842, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Onishi
authors.affiliation: Department of Infectious Disease Control, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: The Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8560, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Chubu Rosai Hospital, Japan Labour Health and Welfare Organization, 1-10-6 Komei, Minato-ku, Nagoya, Aichi 455-8530, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
authors.affiliation: Department of Chemistry, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Naoji
authors.initials: N
authors.lastname: Kubota
keywords: artificial enzyme; diethylaminoethyl–dextran–MMA; graft copolymer; multi-drug resistance of cancer cells; paclitaxel; supramolecular complex