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

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A robust control system for targeting melanoma by a supermolecular DDMC/paclitaxel complex
Integrative Biology ( IF 1.5 ) Pub Date : 2018-08-24 , DOI: 10.1039/c8ib00071a
Y. Onishi _{1,

2,

3} , Y. Eshita _{3,

4,

5,

6,

7} , R.-C. Ji _{3,

6,

8,

9,

10} , T. Kobayashi _{3,

4,

5,

6,

7} , M. Onishi _{1,

2,

3} , M. Mizuno _{3,

11,

12,

13} , J. Yoshida _{3,

14,

15} , N. Kubota _{3,

5,

6,

7,

16}

Affiliation

Ryujyu Science Corporation
Seto
Japan
Department of Infectious Disease Control
Faculty of Medicine
Oita University
Yufu
Department of Human Anatomy
Oita University Faculty of Medicine
Faculty of Welfare and Health Science
The Center for Advanced Medicine and Clinical Research
Nagoya University Hospital
Nagoya
Sakura General Hospital
Ōguchi
Department of Chemistry

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”.

中文翻译：

通过超分子DDMC /紫杉醇复合物靶向黑色素瘤的强大控制系统

使用PTX作为客体和DDMC作为主体，制备了DEAE-葡聚糖-MMA共聚物（DDMC）-紫杉醇（PTX）共轭物。证实了B16F10黑色素瘤细胞对PTX的抗性，而DDMC-PTX共轭物则具有遵循Hill方程的优异抗癌活性。通过BIBO稳定性证实了变构系统的肿瘤微环境中的鲁棒性。通过传递函数解释的这种反馈控制系统非常稳定，并通过回路显示了该系统的可持续性，并且显示了优异的抗癌活性，而没有癌细胞的耐药性。该信号系统在肿瘤微环境中的框图使用其环路传递函数G（s）和外力的d N（s）。这种独立的响应是理想的响应，没有出口响应的时间滞后。DDMC–PTX的细胞死亡率更依赖于希尔系数n而不是米氏常数K _m。这意味着这种与微管蛋白的超分子反应遵循“诱导拟合模型”。

更新日期：2018-08-24

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