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Development of β-elemene and Cisplatin Co-Loaded Liposomes for Effective Lung Cancer Therapy and Evaluation in Patient-Derived Tumor Xenografts

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Abstract

Purpose

β-elemene and cisplatin combined chemotherapy currently is one of the most important settings available for lung cancer therapy in China. However, the clinical outcome is limited by their pharmacokinetic drawbacks. On the other hand, most of nanomedicines have failed in clinical development due to the huge differences between heterogeneous clinical tumor tissues and homogenous cell-derived xenografts. In this work, we fabricated a β-elemene and cisplatin co-loaded liposomal system to effectively treat lung cancer.

Method

In vitro cytotoxicity of co-loaded liposomes was studied by MTT, trypan and Hoechst/PI staining, and western blot in A549, A549/DDP, and LCC cells. In vivo antitumor efficacy was evaluated in cell-derived and clinically relevant patient-derived xenografts.

Results

Co-loaded liposomes were more cytotoxic to cancer cells, especially than the combination of single-loaded liposomes, benefiting from their simultaneous drug internalization and release. As a result, they exhibited desirable therapeutic outcome in both cell-derived and patient-derived xenografts.

Conclusion

β-elemene and cisplatin co-loaded liposomes are a clinically promising candidate for effective lung cancer therapy.

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Abbreviations

β-ELE:

β-elemene

CDX:

Cell-derived xenograft

Chol:

Cholesterol

DDP:

Cisplatin

LPs:

Liposomes

PC:

Phosphatidylcholine

PDX:

Patient-derived xenograft

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Acknowledgments and Disclosures

The work was supported by the National Natural Science Foundation of China (81,401,506 and 61,571,245), Natural Science Foundation of Jiangsu Province of China (BK20161283), Jiangsu Province “Six Summit Talent” Foundation (2016-YY-061), Applied Basic Research Project Foundation of Nantong (MS12016024 and MS22016066), and Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents.

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Author notes

  1. Mingxiang Cao and Mengmeng Long contributed equally to this work.

Authors and Affiliations

  1. Institute of Special Environmental Medicine, Nantong University, Nantong, People’s Republic of China

    Mingxiang Cao, Mengmeng Long, Yapeng Lu, Qianqian Luo, Yue Zhao, Ailing Lu, Cunwang Ge, Li Zhu & Zhongping Chen

  2. Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China

    Qiuping Chen

  3. Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA

    Zhongping Chen

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  1. Mingxiang Cao
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  2. Mengmeng Long
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Correspondence to Zhongping Chen.

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Cao, M., Long, M., Chen, Q. et al. Development of β-elemene and Cisplatin Co-Loaded Liposomes for Effective Lung Cancer Therapy and Evaluation in Patient-Derived Tumor Xenografts. Pharm Res 36, 121 (2019). https://doi.org/10.1007/s11095-019-2656-x

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