Biodegradable Polydisulfide Dendrimer Nanoclusters as MRI Contrast Agents

Abstract

Gd-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 pre-metalated 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.

Gd-based Macromolecules and Nanoparticles as Magnetic Resonance Contrast Agents for Molecular Imaging

“…Due to their high relaxivity, DNCs functionalized with folic acid were capable of specifically detecting folate receptor-positive tumors in mouse xenografts. More recently, it has been shown that biodegradable polydisulfide DNCs can also be formed, through the use of PEG-disulfide linkers[59]. These agents exhibited a serum half-life of 1.6 hrs and low tissue retention at 24 hours.…”

Mesoporous silica nanoparticles functionalized with fluorescent and MRI reporters for the visualization of murine tumors overexpressing αvβ3receptors

“…For example, nanomaterials, such as dendrimers, 5 polymers, [6][7] proteins, 8 gold 9 and silica [10][11] nanoparticles have been applied as slowly moving carriers for Gd(III)-complexes. One of the most significant limitation of the currently reported nanosized T 1 -CAs is their large overall size (>100 nm) that markedly affect their in vivo distribution as they are quickly cleared by the reticuloendothelial system (RES).…”

Bio-Inspired Supramolecular Hybrid Dendrimers Self-Assembled from Low-Generation Peptide Dendrons for Highly Efficient Gene Delivery and Biological Tracking

“…On one hand, cross-linking low-generation poly(amido amine) (PAMAM) dendrimers via bioreducible covalent bonds has generated some efficient and biocompatible nanocarriers which are obviously superior to classic high-generation dendrimers. 7,8 On the other hand, in recent years, self-assembly of dendrimers and dendrons via noncovalent interactions has attracted significant attention from researchers in chemistry and materials science to construct supramolecular dendritic systems mimicking natural sophisticated nanostructures with excellent performance. 9,10 Especially in the biomedical field, self-assembling amphiphilic dendrons and dendrimers into supramolecular dendritic systems is the most promising chemical strategy to generate the latest delivery nanoplatforms, 11,12 which have held great potential for the therapeutic delivery of drugs, 13À15 genes, 16À18 vaccines, 19 and molecular probes.…”