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    Research Article

    Loading Lovastatin into Camptothecin–Floxuridine Conjugate Nanocapsules for Enhancing Anti-metastatic Efficacy of Cocktail Chemotherapy on Triple-negative Breast Cancer
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    • Nisi Zhang
      Nisi Zhang
      Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
      More by Nisi Zhang
    • Xiaolong Liang
      Xiaolong Liang
      Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China
      More by Xiaolong Liang
    • Chuang Gao
      Chuang Gao
      Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
      More by Chuang Gao
    • Min Chen
      Min Chen
      Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
      More by Min Chen
    • Yiming Zhou
      Yiming Zhou
      Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
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    • Christopher J. Krueger
      Christopher J. Krueger
      Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
      Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
      More by Christopher J. Krueger
    • Gang Bao
      Gang Bao
      Department of Bioengineering, College of Engineering, Rice University, Houston, Texas 77005, United States
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    • Zhuoran Gong
      Zhuoran Gong
      Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
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    • Zhifei Dai*
      Zhifei Dai
      Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China
      *E-mail: [email protected]
      More by Zhifei Dai
      Orcidhttp://orcid.org/0000-0001-6231-3692
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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2018, 10, 35, 29385–29397
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    https://doi.org/10.1021/acsami.8b11723
    Published August 10, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    Triple-negative breast cancer (TNBC) is a malignant and refractory disease with high morbidity and mortality. The TNBC shows no response to hormonal therapy nor targeted therapy due to the lack of known targetable biomarkers. Furthermore, the TNBC also exhibits a high degree of heterogeneity that leads to cancer evolution, drug resistance, metastatic progression, and recurrence, arising from the tumor-initiating properties of cancer stem cells (CSCs). Thus, the development of radical therapeutic regimens with high efficacy and limited side effects is crucial. In this study, we designed an innovative ternary cocktail chemotherapy by using Lovastatin (L)-loaded Janus camptothecin–floxuridine conjugate (CF) nanocapsules (NCs) with ultrahigh drug loading capacity. The obtained LCF NCs were shown to be able to suppress growth of TNBC, including inhibition of growth and metastasis of CSCs, both in vitro and in tumor-bearing mice. Moreover, in animal experiments, the LCF NCs showed sustained and synchronous drug release (half-life > 300 min), 85.2% reduction in pulmonary metastases, and no cancer recurrence during one-month observation post-treatment. Thus, this innovative LCF NC design provides a simple and synergistic strategy for the development of simultaneous triple chemotherapy and could be an efficacious, safe, and amenable choice with higher therapeutic relevance and fewer toxic complications than conventional multidrug delivery systems for TNBC treatment in the future.

    Copyright © 2018 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsami.8b11723.

    • Optimization and Characterization of LCF NCs (Table S1, Figure S1); 4T1 cell culture with chemokines and CSC sortation by fluorescence-activated cell sorting (Figure S2); Anticancer efficacy of LCF NCs on 4T1 cell model (Figure S3); Invasive CSCs with immunofluorescence staining of CD44 and MMP-2 (Figure S4); Representative pulmonary sections stained with hematoxylin for metastatic nodule counting (Figure S5); Toxicology Evaluations on LCF-treated mice (Figure S6) (PDF)

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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2018, 10, 35, 29385–29397
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsami.8b11723
    Published August 10, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

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