期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 35, 页码 29385-29397出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b11723
关键词
nanocapsules; lovastatin; camptothecin; floxuridine; triple-negative breast cancer; cocktail chemotherapy
资金
- National Key Research and Development Program of China [2016YFA0201400]
- National project for research and development of major scientific instruments [81727803]
- National Natural Science Foundation of China [81771846, 81571810]
- Beijing Natural Science Foundation Haidian original innovation joint fund [17L20170]
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China [81421004]
- Peking University Third Hospital [BYSY2015023]
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.
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