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Transferrin-functionalised microemulsion co-delivery of β-elemene and celastrol for enhanced anti-lung cancer treatment and reduced systemic toxicity

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Abstract

In this study, we developed an intravenously injectable, transferrin-functionalised microemulsion that simultaneously carries β-elemene and celastrol (called Tf-EC-MEs) for enhanced anti-lung cancer treatment and reduced systemic toxicity. These dual-drug-loaded Tf-EC-MEs not only displayed synergistic antiproliferative effects on cultured cells in vitro, but also showed enhanced efficacy in vivo via active tumour targeting. In preparatory experiments, we found that β-elemene was capable of being used as oil phase, which enhanced drug-loading efficiency and allowed the mass ratio of β-elemene and celastrol to be optimised. In cellular studies, Tf-EC-MEs exhibited significantly improved A549 cellular uptake compared with β-elemene+celastrol (conventional combination treatment) and EC-MEs (non-active targeted treatment), demonstrating remarkable synergistic antiproliferative effects and higher rates of cell apoptosis. In A549-bearing xenograft mouse tumour models, Tf-EC-MEs exhibited enhanced antitumour activity compared to all other treatments. More importantly, Tf-EC-MEs did not cause the obvious systemic toxicity commonly found with mono-celastrol treatment. Collectively, these findings suggest that Tf-EC-MEs are a promising strategy for the combination drug treatment of lung cancer.

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Funding

This work was supported by the National Natural Science Foundation of China (81672423).

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Authors and Affiliations

  1. The Affiliated Sir Run Run Hospital, Nanjing Medical University, Nanjing, 210009, People’s Republic of China

    Qian Zhang

  2. The Affiliated Nanjing Hospital, Nanjing Medical University, Changle road 68, Nanjing, 210009, Jiangsu, People’s Republic of China

    Qian Zhang & Xiufeng Cao

  3. Fourth Military Medical University, Xi’an, 710003, People’s Republic of China

    Xin Tian

  4. Traditional Chinese Medicine Hospital of Shaanxi Province, Xi’an, 710003, People’s Republic of China

    Xin Tian

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  1. Qian Zhang
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Correspondence to Xiufeng Cao.

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Zhang, Q., Tian, X. & Cao, X. Transferrin-functionalised microemulsion co-delivery of β-elemene and celastrol for enhanced anti-lung cancer treatment and reduced systemic toxicity. Drug Deliv. and Transl. Res. 9, 667–678 (2019). https://doi.org/10.1007/s13346-019-00623-4

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