Zeitschrift für Nanomedizin und biotherapeutische Entdeckung
Offener Zugang
ISSN: 2155-983X
ISSN: 2155-983X
Yuki Eshita, Rui-Cheng Ji, Masayasu Onishi, Lucky Ronald Runtuwene, Kaori Noguchi, Takashi Kobayashi, Masaaki Mizuno, Jun Yoshida, Naoji Kubota and Yasuhiko Onishi
A DEAE-dextran-MMA copolymer (DDMC)-paclitaxel(PTX) complex was obtained by using PTX as the guest and DDMC as the host. The resulting nanoparticles of the DDMC/PTX complex were 50-300 nm in diameter and are confirmed to be useful as an anti-cancer drug forming a stable polymeric micelle in water. The drug resistance of B16F10 melanoma cells to paclitaxel was observed using survival curve analysis. On the other hand, there is no drug resistance of melanoma cells to the DDMC/PTX complex. The DDMC/PTX complex showed superior anticancer activity to paclitaxel alone in vitro. The cell death rate was determined using Michaelis-Menten kinetics, as the DDMC/PTX complex promoted allosteric supramolecular reaction to tubulin. The DDMC/PTX complex showed a very superior anti-cancer activity to paclitaxel alone in vivo in mouse skin. The median survival time (MST) of the saline, PTX, DDMC/PTX4 (particle size 50 nm) and DDMC/PTX5 (particle size 290 nm) groups were 120 hours (T/C, 1.0), 176 hours (T/C, 1.46), 328 hours (T/C, 2.73), and 280 hours (T/C, 2.33), respectively. It will be deduced different chemo-effect on melanoma cells between PTX group and DDMC/PTX-treated mice group from this result. From our results, the DDMC/PTX complex was not extensively degraded in cells, and achieved good efficacy as an intact supramolecular anti-cancer agent. The DDMC/PTX complex showed high reactivity and specificity of anti-melanoma cells, depending on its supramolecular facilities. The DDMC/PTX complex represents the efficacy as supramolecular intact such as artificial enzymes having substrate-selective. These supramolecular facilities to melanoma cells will be very helpful to overcome cancer diseases.