Loading Lovastatin into Camptothecin–Floxuridine Conjugate Nanocapsules for Enhancing Anti-metastatic Efficacy of Cocktail Chemotherapy on Triple-negative Breast Cancer
| Autor: | Min Chen, Yiming Zhou, Nisi Zhang, Xiaolong Liang, Chuang Gao, Zhuoran Gong, Gang Bao, Christopher J. Krueger, Zhifei Dai |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Materials science medicine.medical_treatment Antineoplastic Agents Triple Negative Breast Neoplasms Targeted therapy Metastasis Mice 03 medical and health sciences 0302 clinical medicine Breast cancer Nanocapsules Floxuridine Cancer stem cell Cell Line Tumor medicine Animals Humans General Materials Science Lovastatin Triple-negative breast cancer medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Hormonal therapy Camptothecin medicine.drug |
| Zdroj: | ACS Applied Materials & Interfaces. 10:29385-29397 |
| ISSN: | 1944-8252 1944-8244 |
| DOI: | 10.1021/acsami.8b11723 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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