scholarly journals Peptide-Based Soft Hydrogels Modified with Gadolinium Complexes as MRI Contrast Agents

2020 ◽  
Vol 13 (2) ◽  
pp. 19 ◽  
Author(s):  
Enrico Gallo ◽  
Carlo Diaferia ◽  
Enza Di Gregorio ◽  
Giancarlo Morelli ◽  
Eliana Gianolio ◽  
...  

Poly-aromatic peptide sequences are able to self-assemble into a variety of supramolecular aggregates such as fibers, hydrogels, and tree-like multi-branched nanostructures. Due to their biocompatible nature, these peptide nanostructures have been proposed for several applications in biology and nanomedicine (tissue engineering, drug delivery, bioimaging, and fabrication of biosensors). Here we report the synthesis, the structural characterization and the relaxometric behavior of two novel supramolecular diagnostic agents for magnetic resonance imaging (MRI) technique. These diagnostic agents are obtained for self-assembly of DTPA(Gd)-PEG8-(FY)3 or DOTA(Gd)-PEG8-(FY)3 peptide conjugates, in which the Gd-complexes are linked at the N-terminus of the PEG8-(FY)3 polymer peptide. This latter was previously found able to form self-supporting and stable soft hydrogels at a concentration of 1.0% wt. Analogously, also DTPA(Gd)-PEG8-(FY)3 and DOTA(Gd)-PEG8-(FY)3 exhibit the trend to gelificate at the same range of concentration. Moreover, the structural characterization points out that peptide (FY)3 moiety keeps its capability to arrange into β-sheet structures with an antiparallel orientation of the β-strands. The high relaxivity value of these nanostructures (~12 mM−1·s−1 at 20 MHz) and the very low in vitro cytotoxicity suggest their potential application as supramolecular diagnostic agents for MRI.

2020 ◽  
Vol 49 (26) ◽  
pp. 8927-8932
Author(s):  
Kehan Xu ◽  
Na Xu ◽  
Beibei Zhang ◽  
Weijun Tang ◽  
Yun Ding ◽  
...  

Macrocyclic gadolinium(iii) complexes with hyphenated-amino-N-oxide (HAO) type ligand structures are designed as efficient magnetic resonance imaging (MRI) contrast agents (CAs) with high relaxivity and stability.


Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 889 ◽  
Author(s):  
Nina Kostevšek ◽  
Calvin C. L. Cheung ◽  
Igor Serša ◽  
Mateja Erdani Kreft ◽  
Ilaria Monaco ◽  
...  

The majority of the clinically approved iron oxide nanoparticles (IO NPs) used as contrast agents for magnetic resonance imaging (MRI) have been withdrawn from the market either due to safety concerns or lack of profits. To address this challenge, liposomes have been used to prepare IO-based T2 contrast agents. We studied the influence of different phospholipids on the relaxivity (r2) values of magneto-liposomes (MLs) containing magnetic NPs in the bilayer, where a strong correlation between the bilayer fluidity and r2 is clearly shown. Embedding 5-nm IO NPs in the lipid bilayer leads to a significant improvement in their relaxivity, where r2 values range from 153 ± 5 s−1 mM−1 for DPPC/cholesterol/DSPE-PEG (96/50/4) up to 673 ± 12 s−1 mM−1 for DOPC/DSPE-PEG (96/4), compared to “free” IO NPs with an r2 value of 16 s−1 mM−1, measured at 9.4 T MRI scanner. In vitro MRI measurements, together with the ICP-MS analysis, revealed MLs as highly selective contrast agents that were preferentially taken up by cancerous T24 cells, which led to an improvement in the contrast and an easier distinction between the healthy and the cancerous cells. A careful selection of the lipid bilayer to prepare MLs could offer efficient MRI contrast agents, even at very low IO NP concentrations.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
V. Naumenko ◽  
A. Garanina ◽  
A. Nikitin ◽  
S. Vodopyanov ◽  
N. Vorobyeva ◽  
...  

Magnetic resonance imaging (MRI) is a powerful technique for tumor diagnostics. Iron oxide nanoparticles (IONPs) are safe and biocompatible tools that can be used for further enhancing MR tumor contrasting. Although numerous IONPs have been proposed as MRI contrast agents, low delivery rates to tumor site limit its application. IONPs accumulation in malignancies depends on both IONPs characteristics and tumor properties. In the current paper, three differently shaped Pluronic F-127-modified IONPs (nanocubes, nanoclusters, and nanorods) were compared side by side in three murine tumor models (4T1 breast cancer, B16 melanoma, and CT26 colon cancer). Orthotopic B16 tumors demonstrated more efficient IONPs uptake than heterotopic implants. Magnetic nanocubes (MNCb) had the highest r2-relaxivity in vitro (300 mM−1·s−1) compared with magnetic nanoclusters (MNCl, 104 mM−1·s−1) and magnetic nanorods (MNRd, 51 mM−1·s−1). As measured by atomic emission spectroscopy, MNCb also demonstrated better delivery efficiency to tumors (3.79% ID) than MNCl (2.94% ID) and MNRd (1.21% ID). Nevertheless, MNCl overperformed its counterparts in tumor imaging, providing contrast enhancement in 96% of studied malignancies, whereas MNCb and MNRd were detected by MRI in 73% and 63% of tumors, respectively. Maximum MR contrasting efficiency for MNCb and MNCl was around 6-24 hours after systemic administration, whereas for MNRd maximum contrast enhancement was found within first 30 minutes upon treatment. Presumably, MNRd poor MRI performance was due to low r2-relaxivity and rapid clearance by lungs (17.3% ID) immediately after injection. MNCb and MNCl were mainly captured by the liver and spleen without significant accumulation in the lungs, kidneys, and heart. High biocompatibility and profound accumulation in tumor tissues make MNCb and MNCl the promising platforms for MRI-based tumor diagnostics and drug delivery.


2017 ◽  
Vol 3 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Chris J. Zhang ◽  
Michael S. Valic ◽  
Juan Chen ◽  
Gang Zheng

Porphysome nanoparticles are composed of porphyrin-conjugated lipids. The attachment of the porphyrin moiety to each phospholipid confers novel properties to the liposome-like nanoparticle, allowing it to perform a variety of diagnostic and therapeutic applications. The metal chelating properties of porphyrin can be used to bind manganese (Mn), transforming the porphysome into a contrast agent for magnetic resonance imaging (MRI). Previous work has extensively characterized the properties of the Mn-porphysome. Herein, we build upon that work by demonstrating the bio-interactions of Mn-porphysomes in vitro to validate their study in vivo. Particle stability in serum was inferred from fluorescence quenching efficiency, and tolerability to cells was measured using an MTT assay. Mn-porphysomes remained >80% quenched after 14H and showed no toxicity to cells at concentrations below 125 mM. These preliminary results suggest that the porphysome may be used to enhance MRI contrast in vivo.


2019 ◽  
Author(s):  
Simone Schuerle ◽  
Maiko Furubayashi ◽  
Ava P. Soleimany ◽  
Tinotenda Gwisai ◽  
Wei Huang ◽  
...  

AbstractTumor-selective contrast agents have the potential to aid in the diagnosis and treatment of cancer using noninvasive imaging modalities such as magnetic resonance imaging (MRI). Such contrast agents can consist of magnetic nanoparticles incorporating functionalities that respond to cues specific to tumor environments. Genetically engineering magnetotactic bacteria to display peptides has been investigated as a means to produce contrast agents that combine the robust image contrast effects of magnetosomes with transgenic targeting peptides displayed on their surface. This work reports the first use of magnetic nanoparticles that display genetically-encoded pH low insertion peptide (pHLIP), a long peptide intended to enhance MRI contrast by targeting the extracellular acidity associated with the tumors. To demonstrate the modularity of this versatile platform to incorporate diverse targeting ligands by genetic engineering, we also incorporated the cyclic αv integrin-binding peptide iRGD into separate magnetosomes. Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well-suited as T2 contrast agents, while exhibiting increased binding compared to wild-type magnetosomes.


2016 ◽  
Vol 4 (45) ◽  
pp. 7241-7248 ◽  
Author(s):  
Qin Zhu ◽  
Heng Yang ◽  
Yuanyuan Li ◽  
Yu Tian ◽  
Wei Wang ◽  
...  

HP-DO3A-based amphiphilic magnetic resonance imaging (MRI) contrast agents show electrostatic self-assembly ability with polyelectrolytes, good biocompatibility, and significant contrast enhancement in in vivo imaging.


Author(s):  
Anton Popov ◽  
Maxim Artemovich Abakumov ◽  
Irina Savintseva ◽  
Artem Ermakov ◽  
Nelly Popova ◽  
...  

Gd-based complexes are widely used as magnetic resonance imaging (MRI) contrast agents. The safety of previously approved contrast agents is questionable and is being re-assessed. The main causes of concern...


Sign in / Sign up

Export Citation Format

Share Document