Imaging Cells using Intracellular Bimodal Optical and MR contrast agents

摘要: Advances in Magnetic Resonance Imaging (MRI) have revolutionized the way which cellular and physiological processes are being investigated. The specificity sensitivity of MR imaging can be further enhanced by introduction contrast agents (CA). Most available CA like Gd-DTPA, Gd-DOTA non-specific restricted to extracellular space. A new generation intracellular developed for labeling cells specifically coupling with special peptides known as cell penetrating (CPP) that convey cargo molecules attached it across membrane. Amongst large variety CPP available, Tat49-57 peptide (derived from HIV-1 Tat protein) is most intensively studied has high delivery ability vast cargos. It been reported better internalization observed retroinverso isomer using d-form [1] also modifications sequence replacement glutamine (q) ornithine (Orn, o) [2]. We present here synthesis bimodal (magnetic fluorescent) based on Gd-DTPA conjugated a fluorescent dye fluorescein isothiocyanate (FITC) (Figure 1). fragments were synthesized solid phase Fmoc (9fluorenylmethoxycarbonyl) mediated scheme. One lysine residue was coupled fragment linker DTPA dianhydride (via α-amino group) FITC eamino group). conjugates then cleaved phase. After purification reversed-phase HPLC, chelated Gd. products again purified HPLC characterized ESI-MS. obtained tested their efficiency cytotoxicity fluorescence imaging. Orn-d-Tat exhibited much compared d-Tat but accompanied increased toxicity. Also difference mechanism orn-d-Tat CA. To conclude, balance needs maintained between toxicity order obtain proficient used tracking.