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A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy

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  • ReceivedJun 22, 2019
  • AcceptedSep 10, 2019
  • PublishedOct 21, 2019

Abstract

The key to improve the therapeutic efficacy for cancer treatment is to increase the delivery of drugs to tumors. For this purpose, tumor-microenvironment stimuli-responsive materials have great potential. Here, we prepared a new nanomedicine by bonding the conjugate of honokiol (HNK) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to a glutathione (GSH)-responsive nanocarrier, poly(α-lipoic acid) polyethylene glycol. The nanomedicine would disintegrate due to the high level of GSH at the tumor sites, achieving the co-delivery of HNK and DMXAA, and realizing the combination therapy through close-range killing by HNK and long-range striking by DMXAA together. In a murine 4T1 breast tumor model, this strategy exhibited high tumor inhibition rate of 93%, and provided a valuable therapeutic choice for cancer therapy.


Funded by

Ministry of Science and Technology of China(2018ZX09711003-012)

the National Natural Science Foundation of China(51873206,51673189,51829302,51503202,51833010,51520105004)

and the Program of Scientific Development of Jilin Province(20190103033JH)


Acknowledgment

This work was supported by the Ministry of Science and Technology of China (2018ZX09711003-012), the National Natural Science Foundation of China (51873206, 51673189, 51829302, 51503202, 51833010 and 51520105004), and the Program of Scientific Development of Jilin Province (20190103033JH).


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Tang Z and Chen X put forward research ideas. Liu Z designed and synthesized the samples, Si X and Wu J performed some chemical synthesis experiments, Shen N and Zhang D performed the animal experiments; Liu Z wrote the paper with support from Tang Z and Chen X. All authors contributed to the general discussion.


Author information

Zhilin Liu is a PhD candidate at the University of Science and Technology of China. His current research focuses on the tumor-microenvironment responsive nanomedicine of drug delivery system.


Zhaohui Tang is a professor in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His research interests are focused on polymeric carriers for tumor treatment and combinational therapy. He has published more than 100 papers in SCI journals, such as Progress in Polymer Science, Advanced Materials, Advanced Science, Biomaterials, Small and Chemical Science.


Xuesi Chen is a professor in Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. His research interests are focused on polymers chemistry on biomedical polymers, biodegradable polymers for drug/gene controlled release, bone repair parts and tissue engineering scaffolds. He published more than 600 papers in SCI journals, such as Progress in Polymer Science, Advanced Materials, Journal of the American Chemical Society and Advanced Functional Materials. He was authorized more than 200 Chinese invention patents.


Supplement

Supplementary information

Supporting data are available in the online version of the paper.


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