No abstract

The properties of LnIII‐HPDO3A complexes as relaxation enhancers and paraCEST agents are essentially related to the hydroxylpropyl moiety. A series of three HPDO3A derivatives, with small modifications to the hydroxyl arm, were herein investigated to understand how heightened control can be gained over the parameters involved in the design of these agents. A full 1H and 17O‐NMR relaxometric analysis was conducted and demonstrated that increasing the length of the OH group from the lanthanide centre significantly enhanced the water exchange rate of the gadolinium complex, but with a subsequent reduction in kinetic stability. Alternatively, the introduction of an additional methyl group, which increased the steric bulk around the OH moiety, resulted in the formation of almost exclusively the TSAP isomer (95 %) as identified by 1H‐NMR of the europium complex. The gadolinium analogue of this complex also exhibited a very fast water exchange rate, but with no detectable loss of kinetic stability. This complex therefore demonstrates a notable improvement over Gd‐HPDO3A.

The heptadentate gadolinium complex Gd.pDO3A (1.Gd) generates significant 31P nuclear magnetic resonance (NMR) relaxation enhancement of biologically relevant phosphate species; adenosine triphosphate (ATP), phosphocreatine (PCr) and inorganic phosphate.

The Pt IV prodrug iproplatin has been actively loaded into liposomes using a calcium acetate gradient, achieving a 3‐fold enhancement in drug concentration compared to passive loading strategies. A strain‐promoted cycloaddition reaction (azide‐ dibenzocyclooctyne) was used to attach iproplatin‐loaded liposomes L(Pt) to gas‐filled microbubbles (M), forming an ultrasound‐responsive drug delivery vehicle [M−L(Pt)]. Ultrasound‐triggered release of iproplatin from the microbubble‐liposome construct was evaluated in cellulo. Breast cancer (MCF‐7) cells treated with both free iproplatin and iproplatin‐loaded liposome−microbubbles [M−L(Pt)] demonstrated an increase in platinum concentration when exposed to ultrasound. No appreciable platinum uptake was observed in MCF‐7 cells following treatment with L(Pt) only or L(Pt)+ultrasound, suggesting that microbubble‐mediated ultrasonic release of platinum‐based drugs from liposomal carriers enables greater control over drug delivery.

Gadolinium contrast agents that bind to human serum albumin (HSA) can achieve significantly higher relaxivity values and show improved vascular retention time. Most contrast agents of this design are linear...

Magnetic resonance imaging (MRI) contrast agents rely on supramolecular interactions for their function, since they rely on solvent exchange at a coordination complex. This chapter explores the ideas that underpin MRI, and goes on to discuss the importance of complex stability and the challenges inherent to responsive complexes that can detect changes in biology.