Anti-tumor Activity of Biodegradable Polymer-Paclitaxel Conjugate Micelles on H22 Liver Cancer Mice Models

Abstract

Two kinds of paclitaxel (PTX) conjugate nanomicelles were prepared for cell apoptosis and anti-tumor activity evaluation on Lewis lung cancer mice models. One (PTX micelles) was prepared by self-assembling the PTX-conjugate co-polymer, poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate/PTX), and the other (FA-PTX micelles) was by co-assembling a mixture of the folic acid (FA)-carrying co-polymer poly(ethylene glycol)-b-poly(L-lactide-co-2,2-dihydroxylmethyl-propylene carbonate/FA) (PEG-b-P(LA-co-DHP/FA)), and the PTX-conjugate co-polymer. At 7 and 14 days after tail intravenous injection, the mice were killed. The inhibition rates of tumor growth for PTX and FA-PTX micelles were 50 and 90%, respectively, on the day 7, and 33 and 71%, respectively, on the day 14 after drug injection. Flow cytometry analysis showed that the cell apoptosis rates were 43, 54 and 72% for the control group, PTX micelles group and FA-PTX micelles group, respectively, on the day 7, and 16, 25 and 42 on the day 14. With the TUNEL assay, the grey values of PTX micelles and FA-PTX micelles groups were determined to be 61-62% and 43-44%, of that of the control group, on day 7 or day 14, respectively. Therefore, the PTX micelles and the FA-PTX composite micelles significantly inhibited the subcutaneously inoculated Lewis lung cancer and effectively induced the cell apoptosis, and the FA-PTX composite micelles displayed a better efficacy than the PTX-micelles, implying the contribution of the folate-mediated targeting and endocytosis effect. (C) Koninklijke Brill NV, Leiden, 2011