Theranostics 2019; 9(16):4704-4716. doi:10.7150/thno.34588 This issue

Research Paper

MicroRNA Biogenesis is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma

Dan Sun1*, Shuangyan Tan1*, Yanli Xiong1,2, Wenchen Pu1, Jiao Li1, Wei Wei2, Canhua Huang1,3, Yu-Quan Wei1, Yong Peng1✉

1. State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
2. Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.
3. West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Sun D, Tan S, Xiong Y, Pu W, Li J, Wei W, Huang C, Wei YQ, Peng Y. MicroRNA Biogenesis is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma. Theranostics 2019; 9(16):4704-4716. doi:10.7150/thno.34588. Available from

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Graphic abstract

Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality. We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA biogenesis, and discovered the small molecule API-1 as a novel and specific Pin1 inhibitor. Despite its significant anti-HCC activity, the low water solubility and in vivo bioavailability of API-1 limit its clinical application. To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy.

Methods: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP. Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized. The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both in vitro and in vivo. Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically.

Results: API-LP had good formulation characteristics and exhibited an enhanced in vitro activity of suppressing proliferation and migration of HCC cells when compared with free API-1. The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5. Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1. Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice.

Conclusion: The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers.

Keywords: hepatocellular carcinoma, Pin1, API-1, liposome, targeted therapy