DataVXAdvanced MaterialsPaper
journal article·2019-11

Combretastatin A4 Nanodrug‐Induced MMP9 Amplification Boosts Tumor‐Selective Release of Doxorubicin Prodrug

Jian Jiang, Na Shen, Tianyuan Ci, Zhaohui Tang, Zhen Gu, Gao Li, Xuesi Chen

Advanced Materials· Volume 31· Issue 44
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Source abstract

Abstract

Abstract Tumor‐associated enzyme‐activated prodrugs can potentially improve the selectivity of chemotherapeutics. However, the paucity of tumor‐associated enzymes which are essential for prodrug activation usually limits the antitumor potency. A cooperative strategy that utilizes combretastatin A4 nanodrug (CA4‐NPs) and matrix metalloproteinase 9 (MMP9)‐activated doxorubicin prodrug (MMP9‐DOX‐NPs) is developed. CA4 is a typical vascular disrupting agent that can selectively disrupt immature tumor blood vessels and exacerbate the tumor hypoxia state. After treatment with CA4‐NPs, MMP9 expression can be significantly enhanced by 5.6‐fold in treated tumors, which further boosts tumor‐selective active drug release of MMP9‐DOX‐NPs by 3.7‐fold in an orthotopic 4T1 mammary adenocarcinoma mouse model. The sequential delivery of CA4‐NPs and MMP9‐DOX‐NPs exhibits enhanced antitumor efficacy with reduced systemic toxicity compared with the noncooperative controls.
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Research context

Nanomaterials

OpenAlex topics: Protease and Inhibitor Mechanisms · Peptidase Inhibition and Analysis · Ubiquitin and proteasome pathways

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Polymer Ecomaterials Jilin Biomedical Polymers Engineering Laboratory Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun 130022 P. R. China

School of Applied Chemistry and Engineering University of Science and Technology of China Hefei 230026 P. R. China

Department of Bioengineering University of California Los Angeles CA 90095 USA

California NanoSystems Institute (CNSI) Jonsson Comprehensive Cancer Center Center for Minimally Invasive Therapeutics University of California Los Angeles CA 90095 USA

Funding

National Natural Science Foundation of China · Ministry of Science and Technology of the People's Republic of China · People's Government of Jilin Province

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