A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity

Abstract

We introduce a new category of nanoparticle-based T 1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd 3+ ·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd 3+ ·DOTA-encapsulated supramolecular nanoparticles (Gd 3+ ·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd 3+ ·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd 3+ ·DOTA⊂SNPs with an r 1 of 17.3 s −1 mM −1 (ca. 4-fold higher than clinical Gd 3+ chelated complexes at high field strengths) was identified. T 1 -weighted imaging of Gd 3+ ·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd 3+ ·DTPA. A Gd 3+ ·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd 3+ ·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T 1 -weighted imaging after injecting Gd 3+ ·DOTA⊂SNPs but not after injecting Gd 3+ ·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd 3+ ·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis.

Mannose-coated gadolinium liposomes for improved magnetic resonance imaging in acute pancreatitis

“…25,26 It can enhance the T 1 WI contrast for MRI because the unpaired electrons of Gd exhibit strong water proton spin-lattice relaxation effect. 38 T 1 WI spin echo sequences in target organs demonstrated a variable degree of contrast enhancement, which was unrelated to the pancreas histologic structures.…”

“…[22][23][24] The imaging agent we aim to use is gadolinium-diethylenetriaminepentaacetic (Gd-DTPA), a beneficial positive contrast agent with a long history of use in MRI examination of AP. 25,26 Liposomes are promising nanomedicines for targeted drug delivery and imaging. Recently, liposomes have emerged as effective nanocarriers of imaging agents, as they increase the circulation time of loaded drugs and the relaxivity of imaging agents, and are of easy preparation and large-scale production.…”

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

“…[39][40][41][42] Each sample was digested with 0.5 mL of concentrated nitric acid using Microwave Digestion System (Ultra WAVE, Milestone, Milan, Italy). Afterward, 125 μL of solution was pipetted from each digested sample and diluted to a total volume of 5 mL with deionized water, followed by ICP-MS analysis (DRC-II; PerkinElmer Inc., Waltham, MA, USA) in argon gas mode.…”

A High‐Throughput Platform for Formulating and Screening Multifunctional Nanoparticles Capable of Simultaneous Delivery of Genes and Transcription Factors

“…Combining integrated microfluidic technologies [16][17][18][19][20][21][22][23][24][25] with a supramolecular synthetic strategy, [15,[26][27][28][29][30] we demonstrate herein a high-throughput approach for formulating and screening multifunctional supramolecular nanoparticles (MFSNPs) that are capable of simultaneous delivery of gene and functional proteins with superb efficiency and controllable stoichiometry among individual payloads ( Figure 1). As illustrated in Figure 1a, this approach utilized two microfluidic systems including a digital droplet generator (DDG; Supporting Information, Section 1.2-1.5, video available in Supporting Information) [20,22] and a microfluidic cell culture array [31,32] .…”

“…As illustrated in Figure 1a, this approach utilized two microfluidic systems including a digital droplet generator (DDG; Supporting Information, Section 1.2-1.5, video available in Supporting Information) [20,22] and a microfluidic cell culture array [31,32] . To enable the capability of on-chip synthesis of MFSNPs using the DDG, we developed a modular assembly system based on the supramolecular synthetic strategy [15,[26][27][28][29][30] (Figure 1b). By utilizing the molecular recognition between adamantane (Ad) and β-cyclodextrin (CD), a combinatorial library of DNA and proteins-encapsulated MFSNPs was generated by the DDG via systematically altering the ratios among the four functional modules.…”