title: Biodegradable polydisulfide dendrimer nanoclusters as MRI contrast agents.
abstract: Gadolinium-conjugated dendrimer nanoclusters (DNCs) are a promising platform for the early detection of disease; however, their clinical utility is potentially limited due to safety concerns related to nephrogenic systemic fibrosis (NSF). In this paper, biodegradable DNCs were prepared with polydisulfide linkages between the individual dendrimers to facilitate excretion. Further, DNCs were labeled with premetalated Gd chelates to eliminate the risk of free Gd becoming entrapped in dendrimer cavities. The biodegradable polydisulfide DNCs possessed a circulation half-life of >1.6 h in mice and produced significant contrast enhancement in the abdominal aorta and kidneys for as long as 4 h. The DNCs were reduced in circulation as a result of thiol-disulfide exchange, and the degradation products were rapidly excreted via renal filtration. These agents demonstrated effective and prolonged in vivo contrast enhancement and yet minimized Gd tissue retention. Biodegradable polydisulfide DNCs represent a promising biodegradable macromolecular MRI contrast agent for magnetic resonance angiography and can potentially be further developed into target-specific MRI contrast agents.
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Ching-Hui
authors.initials: CH
authors.lastname: Huang
authors.forename: Kido
authors.initials: K
authors.lastname: Nwe
authors.forename: Ajlan
authors.initials: A
authors.lastname: Al Zaki
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsourkas
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics; D050091:Dendrimers; D004220:Disulfides / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics*; D057809:HEK293 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053769:Nanocapsules / Q000737:chemistry; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D004220:Disulfides; D053769:Nanocapsules; D005682:Gadolinium