Anti-tumor activity of folate targeted biodegradable polymer–paclitaxel conjugate micelles on EMT-6 breast cancer model

• Folic acid-bearing polymer–PTX micelles showed higher inhibition rates of tumor growth.
• The percentage of cell apoptosis of M(FA/PTX) was highest among drug groups.
• Bcl-2 expression was down-regulated in the drug group.
• Bax expression was up-regulated in the drug group.
• In M(FA/PTX) group, the survival time was prolonged.

BackgroundPaclitaxel (PTX) is a first line chemotherapy drug for breast cancer. There have been few studies reported concerning the therapeutic efficacy of paclitaxel-conjugated polymeric micelles in breast cancer in vivo.MethodsTwo kinds of PTX conjugate micelles, one of which (M(PTX)) contained 25 wt.% of PTX and the other (M(FA/PTX)) contained 22.5 wt.% of PTX and 1.4 wt.% of folate (FA), were prepared for cell apoptosis and anti-tumor activity evaluation on EMT-6 mice breast cancer models in comparison with 0.9 wt.% saline (control) and equivalent PTX. Cell apoptosis was analyzed by flow cytometry. Breast tumors were examined histologically with H&E staining and immunohistochemically by examining Bax and Bcl-2 expression. The survival status of tumor-bearing mice with different treatments was also examined.ResultsOn day 5 of the drug administration, the average tumor masses were 0.49, 0.33, 0.22, and 0.18 g for the control, PTX, M(PTX) and M(FA/PTX) groups, respectively. The inhibition rates of tumor growth calculated for the three drug groups were 32.6%, 51.6% and 62.3%, respectively. The percentage of cell apoptosis based on flow cytometry was 1.0%, 36.6%, 55.9% and 66.1%, respectively, which showed statistically significant differences (p < 0.05) between three drug groups and the control group. Bcl-2 expression of PTX and M(FA/PTX) groups was lower than control group (p < 0.05). Bax expression of drug groups was higher than control group (p < 0.05). At an equivalent paclitaxel dose of 26.7 mg/kg, the average survival time was 33 days, 31 days, 34 days and 42 days, respectively (p < 0.05).ConclusionThe M(FA/PTX) have better anti-tumor activity and are promising in treatment of human breast cancers.