An ATF24 peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

Bingtao Zhai; Peng Chen; Wengang Wang; Shuiping Liu; Jiao Feng; Ting Duan; Yu Xiang; Ruonan Zhang; Mingming Zhang; Xuemeng Han; Xiaying Chen; Qiujie Li; Guohua Li; Ying Liu; Xingxing Huang; Wenzheng Zhang; Ting Pan; Lili Yan; Ting Jin; Tian Xie; Xinbing Sui

doi:10.20892/j.issn.2095-3941.2020.0454

Cancer Biology & Medicine (Aug 2020)

An ATF24 peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

Bingtao Zhai,
Peng Chen,
Wengang Wang,
Shuiping Liu,
Jiao Feng,
Ting Duan,
Yu Xiang,
Ruonan Zhang,
Mingming Zhang,
Xuemeng Han,
Xiaying Chen,
Qiujie Li,
Guohua Li,
Ying Liu,
Xingxing Huang,
Wenzheng Zhang,
Ting Pan,
Lili Yan,
Ting Jin,
Tian Xie,
Xinbing Sui

Affiliations

Bingtao Zhai: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Peng Chen: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Wengang Wang: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Shuiping Liu: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Jiao Feng: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Ting Duan: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Yu Xiang: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Ruonan Zhang: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Mingming Zhang: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Xuemeng Han: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Xiaying Chen: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Qiujie Li: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Guohua Li: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Ying Liu: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China
Xingxing Huang: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Wenzheng Zhang: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Ting Pan: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Lili Yan: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Ting Jin: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Tian Xie: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China
Xinbing Sui: Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, China

DOI: https://doi.org/10.20892/j.issn.2095-3941.2020.0454
Journal volume & issue: Vol. 17, no. 3
pp. 676 – 692

Abstract

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Objective: In this study, we aimed to develop an amino-terminal fragment (ATF) peptide-targeted liposome carrying β-elemene (ATF24-PEG-Lipo-β-E) for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin (DDP) for bladder cancer treatment. Methods: The liposomes were prepared by ethanol injection and high-pressure microjet homogenization. The liposomes were characterized, and the drug content, entrapment efficiency, and in vitro release were studied. The targeting efficiency was investigated using confocal microscopy, ultra-fast liquid chromatography, and an orthotopic bladder cancer model. The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, and cell apoptosis and cell cycle analyses. The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model. Results: ATF24-PEG-Lipo-β-E had small and uniform sizes (˜79 nm), high drug loading capacity (˜5.24 mg/mL), high entrapment efficiency (98.37 ± 0.95%), and exhibited sustained drug release behavior. ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol (PEG)ylated β-elemene liposomes (PEG-Lipo-β-E). DDP, combined with ATF24-PEG-Lipo-β-E, exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase, and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways. Furthermore, the in vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors, using the combined strategy. Conclusions: The present study provided an effective strategy for the targeted delivery of β-elemene (β-E) to bladder cancer, and a combined strategy for bladder cancer treatment.

Published in Cancer Biology & Medicine

ISSN: 2095-3941 (Print)
Publisher: China Anti-Cancer Association
Country of publisher: China
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.cancerbiomed.org/

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