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Salicylic Acid Conjugated Dendrimers Are a Tunable, High Performance CEST MRI NanoPlatform
journal contribution
posted on 2016-02-24, 00:00 authored by Wojciech G. Lesniak, Nikita Oskolkov, Xiaolei Song, Bachchu Lal, Xing Yang, Martin Pomper, John Laterra, Sridhar Nimmagadda, Michael T. McMahonChemical 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.