Chrysin and Docetaxel Loaded Biodegradable Micelle for Combination Chemotherapy of Cancer Stem Cell.
Pharm Res. 2019 Oct 23 ;36(12):165. Epub 2019 Oct 23. PMID: 31646391
PURPOSE: Cancer stem cells (CSCs) have been suggested to represent the main cause of tumour progression, metastasis and drug resistance. Therefore, these cells can be an appropriate target to improve cancer treatment.
METHODS: A novel biodegradable brush copolymeric micelle was synthesized by the ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The obtained micelle was used for co-delivery of the anticancer drug docetaxel (DTX) and Chrysin (CHS) as an adjuvant on the CSCs originated from Human colon adenocarcinoma cell line. Cancer stem cells were enriched by MACS technique and characterized by flow cytometry analysis against CD133 marker.
RESULTS: Data demonstrated that the micelles harbouring DTX@CHS had potential to reduce cancer stem cell viability compared to free DTX@CHS, single-drug formulations and the control group (p < 0.05). The combination effect of DTX and CHS formulated in micelle was synergistic in CSCs (CI < 1). The reactive oxygen species content was shown to increase after cell treatment with DTX@CHS loaded on micelles (p < 0.05). DTX@CHS-micelles inhibited cancer stem cell migration rate in vitro (p < 0.05), indicating an impaired metastasis activity.
CONCLUSION: In conclusion, the synthesized DOX@CHS-micelles can be applied in the introduction of anticancer agents to resistant cancer population by further investigations.