Multi-cycle chemotherapy with the glycolipid-like polymeric micelles evade cancer stem cell enrichment in breast cancer therapy

Abstract

Multi-cycle chemotherapy is commonly used in the clinic, while the phenomena of enrichment of cancer stem cells (CSCs) and enhanced multi-drug resistance (MDR) are commonly involved. This research was designed for evaluating this successive administration. Chitosan oligosaccharide-g-stearic acid (CSOSA) polymer was used as the drug delivery system (DDS) to perform tri-cycle chemotherapy on a new tumor model induced by mammosphere cells. In vitro, on CSCs enriched mammospheres model, the doxorubicin-loaded CSOSA (CSOSA/DOX) displayed an improved growth inhibition effect measured by acid phosphatase assay (APH). While in vivo, the CSOSA/DOX micelles blocked tumor progression and led to a marked decrease of CSCs proportion as well as MDR capacity. What’s more, the CSOSA/DOX helped decay the microenvironment and attenuate systemic side effects. We concluded that the CSOSA polymer could be a potential DDS for long-term multi-cycle chemotherapy in antitumor research.