Hydrodenticity to Enhance Relaxivity of gadolinium-DTPA Within Crosslinked Hyaluronic Acid Nanoparticles

Russo, Maria; Ponsiglione, Alfonso Maria; Forte, Ernesto; Netti, Paolo A.; Torino, Enza

doi:10.2217/nnm-2017-0098

Cited by 22 publications

(29 citation statements)

References 56 publications

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“…Additionally, Russo et al demonstrated that when Gd-DTPA is encapsulated in polymeric networks, a complex equilibrium is formed by elastic stretches of polymer chains, water osmotic pressure and the hydration degree of Gd-CAs and that this equilibrium is able to boost the relaxivity of Gd-based Contrast Agents. This effect is called Hydrodenticity 58 . The ability of the Hydrodenticity to boost the relaxometric properties of Gd-chelates can, on one side, improve MRI performance and, on the other side, potentially reduce the administered dose of CAs keeping performances unmodified.…”

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confidence: 99%

A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

Tammaro

Polidoro

Romano

et al. 2020

Sci Rep

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The combination of different imaging modalities can allow obtaining simultaneously morphological and functional information providing a more accurate diagnosis. This advancement can be reached through the use of multimodal tracers, and nanotechnology-based solutions allow the simultaneous delivery of different diagnostic compounds moving a step towards their safe administration for multimodal imaging acquisition. Among different processes, nanoprecipitation is a consolidate method for the production of nanoparticles and its implementation in microfluidics can further improve the control over final product features accelerating its potential clinical translation. A Hydrodynamic Flow Focusing (HFF) approach is proposed to produce through a ONE-STEP process Multimodal Pegylated crosslinked Hyaluronic Acid NanoParticles (PEG-cHANPs). A monodisperse population of NPs with an average size of 140 nm is produced and Gd-DTPA and ATTO488 compounds are co-encapsulated, simultaneously. The results showed that the obtained multimodal nanoparticle could work as MRI/Optical imaging probe. Furthermore, under the Hydrodenticity effect, a boosting of the T1 values with respect to free Gd-DTPA is preserved. Multimodal Imaging is a promising approach that allows the combination of different imaging techniques, overcoming limitations proper of every single modality 1,2. For example, recently, Magnetic Resonance Imaging (MRI) and Optical imaging (OI) have been used in combination to obtain the excellent sensitivity of the OI with the high spatial resolution of the MRI 3-5. Image acquisition can occur at different times (asynchronously) requiring post-processing analyses performed through digital image manipulation techniques; however, the best consistency both in time and space is achieved when images are simultaneously acquired (synchronously) 6. Despite the great advantages in the Hardware developments, probes able to support simultaneous acquisitions are still missing. Indeed, in current clinical practice, a cocktail of diagnostic compounds is injected with extremely high risk for the patient. In this scenario, the possibility to efficiently co-deliver through a single vector, different diagnostic compounds for different imaging modalities represents a key point. This challenge can be adequately tackled by applying nanotechnologies to the medical field 7-9. Indeed, nanosystems can be used as vectors of active agents and their composition, size, shape, and surface chemistry can be finely modulated to obtain the simultaneous delivery of multiple diagnostic compounds with a significant impact on an early and accurate diagnosis 10-12. Nanovectors can provide simultaneous visualization of the diseased site through different innovative imaging techniques, enhanced-circulation time for the diagnostic compounds, controlled release kinetics, and superior dose scheduling for improved patient compliance 13. However, when systemically injected, nanoparticles are immediately sequestered by macrophages

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confidence: 99%

A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

Tammaro

Polidoro

Romano

et al. 2020

Sci Rep

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“…Indeed, hydrogel matrices made up of hydrophilic polymers are able to accumulate a large amount of water inside the structure, increasing interactions between water molecules and the metal chelate and, consequently, promoting a relaxivity boosting of the T1 CAs [ 25 , 26 , 28 – 30 ]. The effect has been very well described by Russo et al in the Hydrodenticity concept [ 31 ]. They synthesized crosslinked Hyaluronic Acid NPs (cHANPs) loaded with Gd-DTPA through a microfluidic flow-focusing process, demonstrating the possibility to improve relaxivity through the tunability of crosslink density, mesh size, hydrophilicity, and loading capability and by changing the process parameters [ 30 ].…”

Section: Gadolinium-based Casmentioning

confidence: 80%

“…Recent examples have proved that it is possible to entrap Gd-based CAs within nanostructures to improve relaxivity without metal complex chemical modification [ 22 – 31 ]. In some cases, as a result of this “peculiar” encapsulation of the CAs, it has also been reported that the characteristic correlation times, as described by the SBM theory, can be strongly modified.…”

Section: Gadolinium-based Casmentioning

confidence: 99%

“…Indeed, the proper control of the structural properties of polymer-based nanohydrogels affects the water molecules' dynamics resulting in a specific condition in a relaxivity boost [ 36 , 37 ]. This effect is called Hydrodenticity [ 31 ]. In particular, when a complex equilibrium between elastodymanic forces of the polymer chains, water osmotic pressure, and hydration degree of Gd-CAs is reached, SBM correlation times go through a change [ 28 ].…”

Section: Gadolinium-based Casmentioning

confidence: 99%

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New Strategies in the Design of Paramagnetic CAs

Smeraldo

Netti

Torino

2020

Contrast Media & Molecular Imaging

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Nowadays, magnetic resonance imaging (MRI) is the first diagnostic imaging modality for numerous indications able to provide anatomical information with high spatial resolution through the use of magnetic fields and gradients. Indeed, thanks to the characteristic relaxation time of each tissue, it is possible to distinguish between healthy and pathological ones. However, the need to have brighter images to increase differences and catch important diagnostic details has led to the use of contrast agents (CAs). Among them, Gadolinium-based CAs (Gd-CAs) are routinely used in clinical MRI practice. During these last years, FDA highlighted many risks related to the use of Gd-CAs such as nephrotoxicity, heavy allergic effects, and, recently, about the deposition within the brain. These alerts opened a debate about the opportunity to formulate Gd-CAs in a different way but also to the use of alternative and safer compounds to be administered, such as manganese- (Mn-) based agents. In this review, the physical principle behind the role of relaxivity and the T1 boosting will be described in terms of characteristic correlation times and inner and outer spheres. Then, the recent advances in the entrapment of Gd-CAs within nanostructures will be analyzed in terms of relaxivity boosting obtained without the chemical modification of CAs as approved in the chemical practice. Finally, a critical evaluation of the use of manganese-based CAs will be illustrated as an alternative ion to Gd due to its excellent properties and endogenous elimination pathway.

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“…In particular, Netti and Torino's group, from the Centre for Advanced Biomaterials for Healthcare, Italian Institute of technology, Napoli, presented a number of studies expected to make clinical impact in the near future. In this special issue, Russo et al describe the effect of hydration of the hydrogel structure/biopolymer matrices, termed 'Hydrodenticity' to improve the relaxometric properties of Gd-DTPA contrast agents used in MRI [5]. In another paper, Russo et hyaluronic acid nanoparticles for theranostic applications [6].…”

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confidence: 99%

Advances in Biomaterial Design and Application for Medical Intervention

Azzawi

2017

Nanomedicine (Lond.)

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Hydrodenticity to Enhance Relaxivity of gadolinium-DTPA Within Crosslinked Hyaluronic Acid Nanoparticles

Abstract: Hydrodenticity explains the boosting (12-times) of the Gd-DTPA relaxivity by tuning hydrogel structural parameters, potentially enabling the reduction of the administration dosage as approved for clinical use. [Formula: see text].

Cited by 22 publications

References 56 publications

A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

A Microfluidic Platform to design Multimodal PEG - crosslinked Hyaluronic Acid Nanoparticles (PEG-cHANPs) for diagnostic applications

New Strategies in the Design of Paramagnetic CAs

Advances in Biomaterial Design and Application for Medical Intervention

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