Surface-engineered dendrimers for dual drug delivery: a receptor up-regulation and enhanced cancer targeting strategy.

The present study is aimed at developing and evaluating a combined strategy of dual drug delivery, receptor up-regulation, and drug targeting. The dendritic architectures were synthesized and characterized by IR, (1)H-NMR, and (13)C-NMR spectroscopy. The pH-responsive simultaneous release behavior of the loaded bioactive from the carrier was also explored. The cell line studies for MTT cytotoxicity, receptor blockade, and receptor up-regulation assays were performed on HeLa cells. Treatment of cells with low concentration of all-trans retinoic acid (ATRA, approximately 1 microM) caused a selective up-regulation of folate receptors by 2.21-folds when compared with that of untreated control, after 48 h. ATRA showed a lag phase of 12 h in up-regulating the folate receptors. After 48 h, the IC(50) value of naked methotrexate (MTX)-ATRA combination and dendrimer-loaded MTX-ATRA combination were found to be approximately 0.1 and 10 microM, respectively, while folate-anchored dendrimer loaded with MTX-ATRA showed a selectively lowered IC(50) value of 0.04 microM. It was concluded that in allied ailments like cancer, the proposed dual-drug delivery modality bearing anti-cancer bioactive in conjunction with folate receptor up-regulating cargo may prove to be a promising approach toward the development of a flourishing cancer therapy.