title: Salicylic Acid Conjugated Dendrimers Are a Tunable, High Performance CEST MRI NanoPlatform.
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.
authors.forename: Wojciech G
authors.initials: WG
authors.lastname: Lesniak
authors.forename: Nikita
authors.initials: N
authors.lastname: Oskolkov
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Song
authors.forename: Bachchu
authors.initials: B
authors.lastname: Lal
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.forename: Martin
authors.initials: M
authors.lastname: Pomper
authors.forename: John
authors.initials: J
authors.lastname: Laterra
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.affiliation: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute , Baltimore, Maryland 21287, United States.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D064593:Heterografts; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D009368:Neoplasm Transplantation; D020156:Salicylic Acid / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003287:Contrast Media; D050091:Dendrimers; C104700:PAMAM Starburst; D020156:Salicylic Acid
keywords: CED; chemical exchange saturation transfer (CEST); dendrimers; glioblastoma; salicylic acid