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Medium-chain triglyceride-stabilized docetaxel-loaded HSA nanoparticles effectively inhibited metastatic non-small cell lung cancer

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Abstract

Metastatic non-small cell lung cancer (NSCLC) is refractory with a very poor prognosis. Docetaxel (DTX) injection (Taxotere®) has been approved for the treatment of locally advanced or metastatic NSCLC. However, its clinical application is restricted by severe adverse effects and non-selective tissue distribution. In this study, we successfully developed DTX-loaded human serum albumin (HSA) nanoparticles (DNPs) with modified Nab technology, by introducing medium-chain triglyceride (MCT) as a stabilizer. The optimized formulation had a particle size of approximately 130 nm and a favorable stabilization time of more than 24 h. DNPs dissociated in circulation in a concentration-dependent manner and slowly released DTX. Compared with DTX injection, DNPs were more effectively taken up by NSCLC cells, thus exerting stronger inhibitory effects on their proliferation, adhesion, migration, and invasion. In addition, DNPs showed prolonged blood retention and increased tumor accumulation relative to DTX injection. Ultimately, DNPs produced more potent inhibitory effects on primary or metastatic tumor foci than DTX injections but caused markedly lower organ toxicity and hematotoxicity. Overall, these results support that DNPs hold great potential for the treatment of metastatic NSCLC in clinical.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the Shanghai Municipal Natural Science Foundation (19ZR1406200) and the National Natural Science Foundation of China (Grant No. 81872428 and 81703010).

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Author notes

  1. Yunlong Cheng and Xiaoying Pang contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, 201203, China

    Yunlong Cheng, Jing Wu, Lingling Zhou, Jinxu Cao, Liuchang Wang, Kang Qian, Peng Yang, Minjun Xu, Dongyu Sheng, Ran Meng, Pengzhen Wang, Qian Guo, Shuting Xu & Qizhi Zhang

  2. Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China

    Yan Wei

  3. Department of Pharmacy, the Obstetrics and Gynecology Hospital, Fudan University, 200011, Shanghai, China

    Xiaoying Pang

Authors
  1. Yunlong Cheng
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  4. Lingling Zhou
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  9. Minjun Xu
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  15. Yan Wei
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  16. Qizhi Zhang
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Contributions

Yunlong Cheng: methodology, software, validation, formal analysis, investigation, and writing — original draft. Xiaoying Pang: methodology, software, validation, resources, formal analysis, and investigation. Jing Wu: methodology, software, validation, resources, and formal analysis. Lingling Zhou: methodology, software, and validation. Jingxu Cao, Liuchang Wang, Kang Qian, Peng Yang, Minjun Xu, Dongyu Sheng, Ran Meng, Pengzhen Wang, Qian Guo, and Shuting Xu: methodology and validation. Yan Wei: conceptualization, resources, and writing — review and editing, and funding acquisition. Qizhi Zhang: conceptualization; resources; writing, review and editing; supervision; project administration; and funding acquisition. All authors reviewed the results and approved the final version of the manuscript.

Corresponding authors

Correspondence to Yan Wei or Qizhi Zhang.

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Ethics approval and consent to participate

Ethical approval to conduct the study was obtained from the Institutional Animal Care and Use Committee (IACUC) of the School of Pharmacy, Fudan University (approval number: SYXK(Hu) 2015–0023).

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Not applicable.

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The authors declare no competing interests.

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Cheng, Y., Pang, X., Wu, J. et al. Medium-chain triglyceride-stabilized docetaxel-loaded HSA nanoparticles effectively inhibited metastatic non-small cell lung cancer. Drug Deliv. and Transl. Res. 13, 2869–2884 (2023). https://doi.org/10.1007/s13346-023-01355-2

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