Systematic overview of soft materials as a novel frontier for MRI contrast agents

Gallo, Enrico; Rosa, Elisabetta; Diaferia, Carlo; Rossi, Filomena; Tesauro, Diego; Accardo, Antonella

doi:10.1039/d0ra03194a

Cited by 14 publications

(11 citation statements)

References 93 publications

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“…The cell entry pathway is certainly affected by the nanoparticles’ features, including their size and shape, core-corona structure, surface chemistry and charge, hydrophobicity, and mechanical properties [ 10 ]. Another important advantage deriving from the employment of nanoparticles is represented by their capability to simultaneously encapsulate multiple copies of different biologically relevant molecules (contrast agents, organic or metallic drugs, and nucleic acids) [ 11 , 12 , 13 ]. The loading into the inner compartments of the nanoparticles allows them to preserve the bioactive ingredients from potential inactivation they can undergo in the bloodstream.…”

Section: Introductionmentioning

confidence: 99%

Caveolin-Mediated Internalization of Fmoc-FF Nanogels in Breast Cancer Cell Lines

Smaldone¹,

Rosa

Gallo³

et al. 2023

Pharmaceutics

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Introduction: Hydrogel nanoparticles, also known as nanogels (NGs), have been recently proposed as alternative supramolecular vehicles for the delivery of biologically relevant molecules like anticancer drugs and contrast agents. The inner compartment of peptide based NGs can be opportunely modified according to the chemical features of the cargo, thus improving its loading and release. A full understanding of the intracellular mechanism involved in nanogel uptake by cancer cells and tissues would further contribute to the potential diagnostic and clinical applications of these nanocarriers, allowing the fine tuning of their selectivity, potency, and activity. The structural characterization of nanogels were assessed by Dynamic Light Scattering (DLS) and Nanoparticles Tracking Analysis (NTA) analysis. Cells viability of Fmoc-FF nanogels was evaluated by MTT assay on six breast cancer cell lines at different incubation times (24, 48, and 72 h) and peptide concentrations (in the range 6.25 × 10−4 ÷ 5·10−3 × wt%). The cell cycle and mechanisms involved in Fmoc-FF nanogels intracellular uptake were evaluated using flow cytometry and confocal analysis, respectively. Fmoc-FF nanogels, endowed with a diameter of ~130 nm and a zeta potential of ~−20.0/−25.0 mV, enter cancer cells via caveolae, mostly those responsible for albumin uptake. The specificity of the machinery used by Fmoc-FF nanogels confers a selectivity toward cancer cell lines overexpressing the protein caveolin1 and efficiently performing caveolae-mediated endocytosis.

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Section: Introductionmentioning

confidence: 99%

Caveolin-Mediated Internalization of Fmoc-FF Nanogels in Breast Cancer Cell Lines

Smaldone¹,

Rosa

Gallo³

et al. 2023

Pharmaceutics

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“…Clinical visualization of NIR-labeled fibrin using planar imaging optics is restricted to superficial and intraoperative use due to the current technological limitations on optical imaging resolution at the tissue depths needed for noninvasive monitoring. By contrast, magnetic resonance imaging (MRI) is more widely used than fluorescence imaging for implanted, contrast agent-incorporating, degradable bioactive materials 25 and in practice has no depth penetration limits, enabling noninvasive monitoring of degradation during tissue regeneration. However, MRI currently has a spatial resolution limit on the order of 1 mm (for clinical MRI: 0.1 mm for small animal MRI), preventing detailed cellular and subcellular imaging.…”

Section: Discussionmentioning

confidence: 99%

In vivo near-infrared fluorescent fibrin highlights growth of nerve during regeneration across a nerve gap

et al. 2022

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“…[18] In the second case, some studies have been carried out on NGs covalently functionalized with Gd(III) chelates or containing paramagnetic ions that act as structural cross-linking agents. [17,[20][21][22] However, studies of these systems are limited and unsystematic, with rare investigations of their use in vivo as MRI probes. In addition, such nanoparticles showed dimensions greater than 50 nm and relaxivity values at clinical fields lower than those observed for type 1 nanogels.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, such nanoparticles showed dimensions greater than 50 nm and relaxivity values at clinical fields lower than those observed for type 1 nanogels. [22] It is worth mentioning that some toxicity problems associated with the use of Gd-based contrast agents have been reported in patients with renal insufficiency, who can develop a sometimes fatal disease known as nephrogenic systemic fibrosis (NSF). [23] In more recent years, the proven long-term deposition of very low amounts of gadolinium in the brain and other tissues has also raised some concerns about the use of this class of contrast agents, especially in the case of multiple administrations.…”

Section: Introductionmentioning

confidence: 99%

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Novel Nanogels Loaded with Mn(II) Chelates as Effective and Biologically Stable MRI Probes

Carniato

Ricci

Tei

et al. 2023

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Here it is described nanogels (NG) based on a chitosan matrix, which are covalently stabilized by a bisamide derivative of Mn‐t‐CDTA (t–CDTA = trans‐1,2‐diaminocyclohexane‐N,N,N′,N′‐tetraacetic acid). the Mn(II) complex acts both as a contrast medium and as a cross‐linking agent. These nanogels are proposed as an alternative to the less stable paramagnetic nanogels obtained by electrostatic interactions between the polymeric matrix and paramagnetic Gd(III) chelates. The present novel nanogels show: i) relaxivity values seven times higher than that of typical monohydrated Mn(II) chelates at the clinical fields, thanks to the combination of a restricted mobility of the complex with a fast exchange of the metal‐bound water molecule; ii) high stability of the formulation over time at pH 5 and under physiological conditions, thus excluding metal leaking or particles aggregation; iii) good extravasation and accumulation, with a maximum contrast achieved at 24 h post‐injection in mice bearing subcutaneous breast cancer tumor; iv) high T1 contrast (1 T) in the tumor 24 h post‐injection. These improved properties pave the way for the use of these paramagnetic nanogels as promising magnetic resonance imaging (MRI) probes for in vitro and in vivo preclinical applications.

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Systematic overview of soft materials as a novel frontier for MRI contrast agents

Abstract: Gd(iii)-nanostructurated Constrast Agents (CAs) for Magnetic Resonance Imaging (MRI) can be designed and developed by manipulating soft material, including fibers, hydrogels and nanogels, in the nanometer scale.

Cited by 14 publications

References 93 publications

Caveolin-Mediated Internalization of Fmoc-FF Nanogels in Breast Cancer Cell Lines

Caveolin-Mediated Internalization of Fmoc-FF Nanogels in Breast Cancer Cell Lines

In vivo near-infrared fluorescent fibrin highlights growth of nerve during regeneration across a nerve gap

Novel Nanogels Loaded with Mn(II) Chelates as Effective and Biologically Stable MRI Probes

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