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.
摘要
提高肿瘤治疗效果的关键在于增加药物肿瘤部位递送. 为此, 肿瘤微环境刺激响应性材料具有很大的潜力. 本文通过将和厚朴酚和DMXAA缀合物键合到GSH响应性聚硫辛酸-聚乙二醇纳米载体上, 制备出一种新型纳米药物. 在肿瘤部位高谷胱甘肽水平时纳米药物解体, 实现和厚朴酚与DMXAA在肿瘤部位的共同递送. 通过和厚朴酚的近程攻击与DMXAA的远程杀伤, 协同治疗乳腺癌. 在小鼠4T1乳腺肿瘤模型中, 该策略显示肿瘤抑制率高达93%, 为肿瘤治疗提供了有价值的候选治疗方案.
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22 April 2020
In the version of the article originally published in the volume 63, issue 2, 2020 of <Emphasis Type="Italic">Sci China Mater</Emphasis> (2020, 63 (2): 307–315, <ExternalRef><RefSource>https://doi.org/10.1007/s40843-019-1183-0</RefSource><RefTarget Address="10.1007/s40843-019-1183-0" TargetType="DOI"/></ExternalRef>), the affiliations of two of the authors (Zhaohui Tang and Xuesi Chen) were incompletely labeled. The corrected version of the authors’ affiliations is as below: Zhilin Liu<Superscript>1,2</Superscript>, Zhaohui Tang<Superscript>1,2*</Superscript>, Dawei Zhang<Superscript>1</Superscript>, Jiatan Wu<Superscript>3</Superscript>, Xinghui Si<Superscript>1,2</Superscript>, Na Shen<Superscript>1</Superscript> and Xuesi Chen<Superscript>1,2*</Superscript>
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Acknowledgements
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).
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Author contributions 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.
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Conflict of interest The authors declare that they have no conflict of interest.
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.
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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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Liu, Z., Tang, Z., Zhang, D. et al. A novel GSH responsive poly(alpha-lipoic acid) nanocarrier bonding with the honokiol-DMXAA conjugate for combination therapy. Sci. China Mater. 63, 307–315 (2020). https://doi.org/10.1007/s40843-019-1183-0
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DOI: https://doi.org/10.1007/s40843-019-1183-0