A specific micro-RNA (miRNA), microRNA 21 (miR-21), is strongly overexpressed in breast cancer cells. Antisense inhibition of miRNA function, an important tool for uncovering miRNA biology, which is often used to knockdown miRNA, can cause a notable inhibition of cell growth. In this study, 5-fluorouracil (5-FU) was conjugated to polyamidoamine dendrimers via direct encapsulation; this method was then combined with antisense micro-RNA 21 (as-miR-21) strategies to evaluate the effects of the growth suppression of breast cancer cells. Our results show that as-miR-21 strategies significantly improved the chemosensitivity of free 5-FU on breast cancer cells (MCF-7). In addition, not only could as-miR-21 effectively increase the apoptotic cell numbers but it could also bring down the migration ability of MCF-7 cells. Our results provide invaluable information for the future design of drug-polymer complexes for multimodal cancer treatments. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 114: 3760-3766, 2009