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Lovastatin into Camptothecin–Floxuridine
Conjugate Nanocapsules for Enhancing Anti-metastatic Efficacy of Cocktail
Chemotherapy on Triple-negative Breast Cancer
posted on 2018-08-10, 00:00authored byNisi Zhang, Xiaolong Liang, Chuang Gao, Min Chen, Yiming Zhou, Christopher J. Krueger, Gang Bao, Zhuoran Gong, Zhifei Dai
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.