Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically

Liuyun Gong; Yinliang Lu; Jing Wang; Xinyue Li; Jing Zhao; Yuetong Chen; Rongze Ma; Jinlu Ma; Tianya Liu; Suxia Han

doi:10.1016/j.jpha.2023.04.017

Volume 13 Issue 6

Jun. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(6): 603-615

Liuyun Gong, Yinliang Lu, Jing Wang, Xinyue Li, Jing Zhao, Yuetong Chen, Rongze Ma, Jinlu Ma, Tianya Liu, Suxia Han. Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically[J]. Journal of Pharmaceutical Analysis, 2023, 13(6): 603-615. doi: 10.1016/j.jpha.2023.04.017

Citation:

Liuyun Gong, Yinliang Lu, Jing Wang, Xinyue Li, Jing Zhao, Yuetong Chen, Rongze Ma, Jinlu Ma, Tianya Liu, Suxia Han. Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically[J]. Journal of Pharmaceutical Analysis, 2023, 13(6): 603-615. doi: 10.1016/j.jpha.2023.04.017

Citation:

Liuyun Gong, Yinliang Lu, Jing Wang, Xinyue Li, Jing Zhao, Yuetong Chen, Rongze Ma, Jinlu Ma, Tianya Liu, Suxia Han. Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically[J]. Journal of Pharmaceutical Analysis, 2023, 13(6): 603-615. doi: 10.1016/j.jpha.2023.04.017

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Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically

doi: 10.1016/j.jpha.2023.04.017

a. Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China;
b. National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China;
c. Department of Radiotherapy, The First Affiliated Hospital Soochow University, Suzhou, Jiangsu, 215000, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant Nos.: 81272488 and 81602802) and the Shaanxi Province Innovation Capacity Support Program (Grant No.: 2018TD-002). We thank Mr. Xiaofei Wang et al. at the Experimental Biomedical Center of Xi'an Jiaotong University for their kind assistance with the instrument operation and data analysis.

Received Date: Mar. 19, 2023
Accepted Date: Apr. 24, 2023
Rev Recd Date: Apr. 19, 2023
Publish Date: Apr. 28, 2023

Abstract

Abstract

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic agents. To overcome it, the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a nano-carrier. Herein, a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular compound. In this proof-of-concept study, the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1 (XPO1) and ataxia telangiectasia mutated-Rad3-related (ATR), and then a super-assembled nano-pill (gold nano drug carrier loaded AZD6738 and 97−110 amino acids of apoptin (AP) (AA@G)) was constructed through camouflaging AZD6738 (ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular nanoparticle. As expected, both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest, promoting DNA damage and inhibiting DNA repair of hepatoma cell. This work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential, but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds, thereby extending the scope of drugs for developing the advanced combination therapy.
- Liver cancer,
- Drug combination,
- Cancer therapy,
- ATR inhibitor,
- XPO1 inhibitor

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