Salicylic Acid Conjugated Dendrimers Are a Tunable, High Performance CEST MRI NanoPlatform

Nano Lett. 2016 Apr 13;16(4):2248-53. doi: 10.1021/acs.nanolett.5b04517. Epub 2016 Mar 1.

Abstract

Chemical exchange saturation transfer (CEST) is a novel MRI contrast mechanism that is well suited for imaging, however, existing small molecule CEST agents suffer from low sensitivity. We have developed salicylic acid conjugated dendrimers as a versatile, high performance nanoplatform. In particular, we have prepared nanocarriers based on generation 5-poly(amidoamine) (PAMAM) dendrimers with salicylic acid covalently attached to their surface. The resulting conjugates produce strong CEST contrast 9.4 ppm from water with the proton exchange tunable from ∼1000 s(-1) to ∼4500 s(-1) making these dendrimers well suited for sensitive detection. Furthermore, we demonstrate that these conjugates can be used for monitoring convection enhanced delivery into U87 glioblastoma bearing mice, with the contrast produced by these nanoparticles persisting for over 1.5 h and distributed over ∼50% of the tumors. Our results demonstrate that SA modified dendrimers present a promising new nanoplatform for medical applications.

Keywords: CED; chemical exchange saturation transfer (CEST); dendrimers; glioblastoma; salicylic acid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging*
  • Contrast Media* / chemistry
  • Contrast Media* / pharmacology
  • Dendrimers* / chemistry
  • Dendrimers* / pharmacology
  • Glioblastoma / diagnostic imaging*
  • Heterografts
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Neoplasm Transplantation
  • Salicylic Acid* / chemistry
  • Salicylic Acid* / pharmacology

Substances

  • Contrast Media
  • Dendrimers
  • PAMAM Starburst
  • Salicylic Acid