Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 8, Pages 7022-7030Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b01633
Keywords
cancer stem cells; cerasome; lovastatin; triple-negative breast cancer; epithelial-to-mesenchymal transition
Funding
- National Natural Science Foundation of China [81472496]
- National Key Research and Development Program of China [2016YFA0201400]
- Young Scholar Program of Department of Education of Hunan Province [14B112]
- Key Project of Department of Education of Hunan Province [14A089]
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Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a higher risk in younger women and a poorer prognosis and without targeted therapies available currently. Cancer stem cells (CSCs) are increasingly recognized as the main cause of treatment failure and tumor recurrence. The present paper reports the encapsulation of lovastatin (LV) into cerasomes. Compared with free LV, cerasome-encapsulated LV (C-LV) nanohybrids showed cytotoxicity to MDA-MB-231 CSCs in a dose and time-dependent manner. Furthermore, intravenous injection of C-LV nanohybrids resulted in a significant tumor size reduction in a dose dependent manner in xenograft tumors derived from subcutaneous inoculation of MDA-MB-231 cells. Furthermore, histopathological and/or immunohistochemical analysis revealed that C-LV nanohybrids significantly induced mammary gland formation and apoptosis and inhibited angiogenesis, the CSC phenotype, and the epithelial-to-mesenchymal transition in xenograft tumors. Most importantly, C-LV nanohybrids were found to be more effective than free LV in inhibiting the growth of breast cancer xenografts and the sternness properties in vivo. To the best of our knowledge, ours is the first demonstration of nanohybrids for efficient inhibition of CSCs derived from TNBC, offering a new option for the TNBC treatment.
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