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Bifunctional liposome reduces chemotherapy resistance of doxorubicin induced by tumor hypoxia

Abstract

Doxorubicin (DOX) Liposome is a widely used nano-medicine for colorectal cancer treatment. However, doxorubicin therapy increases the level of reactive oxygen species (ROS) in tumor cells, such as hydrogen peroxide (H2O2), which can stabilize hypoxia-inducible-factor-1α (HIF-1α). In a tumor hypoxic microenvironment, HIF-1 can up-regulate tumor-resistance related proteins, including P-glycoprotein (P-gp), Glucose transporter 1 (GLUT-1), matrix metalloproteinase 9 (MMP-9), leading to tumor tolerance of chemotherapy. The functional inhibition of HIF-1 can overcome this resistance and enhance the efficacy of tumor therapy. Here, we encapsulated one of most effective HIF-1 inhibitors, acriflavine (ACF), and DOX in liposomes (DOX-ACF@Lipo) to construct bifunctional liposomes. ACF and DOX, released from DOX-ACF@Lipo, could effectively suppress the function of HIF-1 and process of DNA replication, respectively. Consequently, the bifunctional liposome has great potential to be applied in clinic to overcome chemotherapy resistance induced by hypoxia.

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Supplementary files

Publication details

The article was received on 12 Apr 2019, accepted on 12 Jul 2019 and first published on 15 Aug 2019


Article type: Paper
DOI: 10.1039/C9BM00590K
Biomater. Sci., 2019, Accepted Manuscript

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    Bifunctional liposome reduces chemotherapy resistance of doxorubicin induced by tumor hypoxia

    L. Xu, Z. Zhang, Y. Ding, L. Wang, Y. Cheng, L. Meng, J. Wu, A. Yuan, Y. Hu and Y. Zhu, Biomater. Sci., 2019, Accepted Manuscript , DOI: 10.1039/C9BM00590K

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