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Temozolomide (TMZ) is a promising chemotherapeutic agent for treating glioblastomas. However, resistance develops quickly and with a high frequency. Efforts to overcome chemoresistance are, therefore, critically needed. In present study, a poly(amidoamine; PAMAM) dendrimer was used as a vector to deliver microRNA-21 inhibitor (miR-21i) into U87 cells and the chemosensitivity of the combination effect of miR-21i and TMZ for glioma therapy was investigated. Flow cytometry analysis showed the uptake efficiency of microRNA-21 inhibitor after complexation with PAMAM. Real-time PCR and in situ hybridization indicated that, compared with TMZ or miR-21i treated cells, cells simultaneously treated with miR-21i and TMZ showed a remarkable decrease in the microRNA-21 (miR-21) level. The transfection of miR-21i enhanced the chemosensitivity by significantly decreasing the IC50 value of TMZ to glioma cells. Knockdown of miR-21 promoted the cells' apoptosis, and at the same time, inhibited cell invasion. In conclusion, the combination treatment of glioma cells with TMZ and miR-21i could yield a synergistic effect in inhibition of human glioma cell line. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2012 [ABSTRACT FROM AUTHOR]