ParaCEST agents encapsulated in Reverse Nano-Assembled Capsules (RACs): How slow molecular tumbling can quench CEST contrast

Annah Farashishiko, Jacqueline R. Slack, Mauro Botta, Mark Woods

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

Original languageEnglish (US)
Article number96
JournalFrontiers in Chemistry
Issue numberAPR
StatePublished - Apr 1 2018


  • Assembled nano-capsules
  • CEST quenching
  • Contrast agents
  • Molecular tumbling
  • NMR relaxation

ASJC Scopus subject areas

  • General Chemistry


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