Magnetic nanocomposites as MRI probes: Design and applications

past decade for integrin-targeted delivery of anticancer agents. In this presentation, design and characterization of amphiphiles composed of different analogs of RGD (linear, cyclic or glycosylated) and aliphatic fatty acid with or without 8-amino-3,6-dioxaoctanoic acid (ADA), as linker will be discussed. The amphiphiles exhibited critical micelle concentration in the range of 7-30 μM. Transmission electron microscopy images showed the formation of spherical micelles in the size range of 10-40 nm. The micelle was formed by association of 12-16 amphiphile molecules. Forster Resonance Energy Transfer studies revealed the entrapment of hydrophobic dyes within the micellar core. The αvβ3 integrin binding specificity of micelles was demonstrated in fluorescence probe displacement study and the cyclic RGD micelles exhibited highest displacement in the study. The internalization of fluorescein isothiocynate (FITC) loaded RGD micelles was significantly higher in A2058 melanoma cells compared to free FITC after incubation at 37 °C. The micelles showed significantly lower internalization at 4 °C when pretreated with 0.45 M sucrose. This result indicated that the endocytosis of RGD micellar carriers occurred in the cellular uptake process. Solubility of paclitaxel was enhanced up to 35 folds using peptide amphiphiles. The IC50 of paclitaxel loaded RGD micelles was decreased in integrin overexpressed A2058 melanoma cells by 1.8 to 3.6 times compared to free drug, while IC50 values increased by 2 to 9 times for paclitaxel loaded RGD micelles in control Detroit 551 cells. Using A2058 melanoma xenograft mice model, the paclitaxel loaded RGD micelles exhibited a significant inhibition of tumor growth in comparison to an equivalent dose of paclitaxel. The studies demonstrated the feasibility of targeted delivery of anticancer agent using peptide amphiphiles.