Hypoxia-targeting dendritic MRI contrast agent based on internally hydroxy dendrimer for tumor imaging

Abstract Hypoxia is one of the critical features in solid tumors, and hypoxia-targeting contrast agents (CAs) could greatly enhance the magnetic resonance imaging (MRI) of tumors by increasing its specificity and providing more diagnosis information. In this article, an internally hydroxy dendrimer of high molecular weight was facilely synthesized by “epoxy-amine” and “thiol-ene” reactions with a β-cyclodextrin (β-CD) as the core, and a hypoxia-targeting dendritic contrast agent (DCA) was synthesized through conjugating Gd chelates onto the internal hydroxyl groups and grafting the hypoxia-targeting groups sulfonamides and zwitterionic groups onto the exterior groups of the dendrimer. The zwitterionic surface without disturbance from internally conjugated CAs could reduce unspecific cellular uptake by normal cells, while the hypoxia-targeting group mediate the cellular uptake by hypoxic tumor cells. The in vitro and in vivo study showed that the hypoxia-targeting DCA could be selectively uptake by hypoxic cancer cells and greatly enhance the MRI of orthotopic breast tumor in a mouse model.