A robust control system for targeting melanoma by a supermolecular DDMC/paclitaxel complex

Abstract

A DEAE–dextran-MMA copolymer (DDMC)–paclitaxel (PTX) conjugate was prepared using PTX as the guest and DDMC as the host. The resistance of B16F10 melanoma cells to PTX was confirmed, while the DDMC–PTX conjugate showed excellent anticancer activity that followed the Hill equation. The robustness in the tumor microenvironment of the allosteric system was confirmed via BIBO stability. This feedback control system, explained via a transfer function, was very stable and showed the sustainability of the system via a loop, and it showed superior anti-cancer activity without drug resistance from cancer cells. The block diagram of this signal system in the tumor microenvironment used its loop transfer function G(s) and the dN(s) of the external force. This indicial response is an ideal one without a time lag for the outlet response. The cell death rate of DDMC–PTX is more dependent on the Hill coefficient n than on the Michaelis constant K_m. This means that this supermolecular reaction with tubulin follows an “induced fit model”.