title: Gadolinium-labeled peptide dendrimers with controlled structures as potential magnetic resonance imaging contrast agents.
abstract: Gadolinium (Gd(3+)) based dendrimers with precise and tunable nanoscopic sizes are excellent candidates as magnetic resonance imaging (MRI) contrast agents. Control of agents' sensitivity, biosafety and functionality is key to the successful applications. We report the synthesis of Gd(III)-based peptide dendrimers possessing highly controlled and precise structures, and their potential applications as MRI contrast agents. These agents have no obvious cytotoxicity as verified by in vitro studies. One of the dendrimer formulations with mPEG modification showed a 9-fold increase in T(1) relaxivity to 39.2 Gd(III) mM(-1) s(-1) comparing to Gd-DTPA. In vivo studies have shown that the mPEGylated Gd(III)-based dendrimer provided much higher signal intensity enhancement (SI) in mouse kidney, especially at 60 min post-injection, with 54.8% relatively enhanced SI. The accumulations of mPEGylated dendrimer in mouse liver and kidney were confirmed through measurement of gadolinium by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Meanwhile, mPEGylated dendrimer showed much higher Gd(III) concentration in blood with 38 μg Gd(III)/g blood at 1 h post-injection comparing to other dendrimer formulations. These findings provide an attractive alternative strategy to the design of multifunctional gadolinium-based dendrimers with controlled structures, and open up possibilities of using the Gd(III)-based peptide dendrimers as MRI probes.
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Luo
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Wenchuan
authors.initials: W
authors.lastname: She
authors.forename: Qiaoying
authors.initials: Q
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Hua
authors.initials: H
authors.lastname: Ai
authors.forename: Qiyong
authors.initials: Q
authors.lastname: Gong
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019786:Gadolinium DTPA / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013194:Staining and Labeling; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D010455:Peptides; D019786:Gadolinium DTPA