PEGylated Crosslinked Hyaluronic Acid Nanoparticles Designed Through a Microfluidic Platform for Nanomedicine

Russo, Maria; Grimaldi, Anna; Bevilacqua, Paolo; Tammaro, Olimpia; Netti, Paolo A.; Torino, Enza

doi:10.2217/nnm-2017-0103

Cited by 16 publications

(17 citation statements)

References 39 publications

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“…For example, regarding inorganic nanoparticles, Kim and co-workers 47 presented nanocomposite microspheres incorporating alginate, iron oxide nanoclusters and Au nanorods for MRI/CT multimodal applications. In another work, using full biocompatible and already approved biomaterials, Russo et al 48 . developed Hyaluronic acid nanoparticles crosslinked through divynilsulfone, encapsulating Gd-DTPA and ATTO633, as a new probe for MRI/Optical combination.…”

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confidence: 99%

“…Starting from the evidence of the previous works related to the crosslinked Hyaluronic Acid NanoParticles (cHANPs) 41,48 we are proposing an innovative process based on HFF to obtain in a ONE-STEP process the crosslinking reaction between thiolated Hyaluronic Acid (HA-SH) and Polyethylene glycol-vinyl sulfone (PEG-VS producing pegylated cHANPs (PEG-cHANPs), to produce multimodal probes for diagnostic applications.…”

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confidence: 99%

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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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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 relaxivity (r 1 ) achieved with the cHANPs is 12-times higher than Gd-DTPA. Within cHANPs, the properties of Hydrodenticity can be modulated to obtain the desired mesh size, crosslink density, hydrophilicity and loading capability, as reported by Russo et al 39, 40. Moreover, they proved that an increase of the crosslinking degree of biopolymer can induce the enhancement of relaxivity by restricting molecular tumbling while maintaining the switching property 41 and allowing easy access of water throughout the structure, which is a key feature in MRI CAs.…”

Section: Introductionmentioning

confidence: 89%

Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA

Ponsiglione¹,

Russo²,

Grimaldi³

et al. 2019

Theranostics

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Recently, rational design of a new class of contrast agents (CAs), based on biopolymers (hydrogels), have received considerable attention in Magnetic Resonance Imaging (MRI) diagnostic field. Several strategies have been adopted to improve relaxivity without chemical modification of the commercial CAs, however, understanding the MRI enhancement mechanism remains a challenge. Methods: A multidisciplinary approach is used to highlight the basic principles ruling biopolymer-CA interactions in the perspective of their influence on the relaxometric properties of the CA. Changes in polymer conformation and thermodynamic interactions of CAs and polymers in aqueous solutions are detected by isothermal titration calorimetric (ITC) measurements and later, these interactions are investigated at the molecular level using NMR to better understand the involved phenomena. Water molecular dynamics of these systems is also studied using Differential Scanning Calorimetry (DSC). To observe relaxometric properties variations, we have monitored the MRI enhancement of the examined structures over all the experiments. The study of polymer-CA solutions reveals that thermodynamic interactions between biopolymers and CAs could be used to improve MRI Gd-based CA efficiency. High-Pressure Homogenization is used to obtain nanoparticles. Results: The effect of the hydration of the hydrogel structure on the relaxometric properties, called Hydrodenticity and its application to the nanomedicine field, is exploited. The explanation of this concept takes place through several key aspects underlying biopolymer-CA's interactions mediated by the water. In addition, Hydrodenticity is applied to develop Gadolinium-based polymer nanovectors with size around 200 nm with improved MRI relaxation time (10-times). Conclusions: The experimental results indicate that the entrapment of metal chelates in hydrogel nanostructures offers a versatile platform for developing different high performing CAs for disease diagnosis.

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“…e production of crosslinked Hyaluronic Acid Nanoparticles is a consolidate process [27][28][29]. Briefly, nanoprecipitation is implemented in an X-junction chip by a hydrodynamic flow focusing regime.…”

Section: Chanps Productionmentioning

confidence: 99%

Targeting Nanostrategies for Imaging of Atherosclerosis

Polidoro

Grassia

Sarno

et al. 2021

Contrast Media & Molecular Imaging

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Despite the progress in cardiovascular research, atherosclerosis still represents the main cause of death worldwide. Clinically, the diagnosis of Atherosclerotic Cardiovascular Disease (ASCVD) relies on imaging methodologies including X-ray angiography and computed tomography (CT), which however still fails in the identification of patients at high risk of plaque rupture, the main cause of severe clinical events as stroke and heart attack. Magnetic resonance imaging, which is characterized by very high spatial resolution, could provide a better characterization of atherosclerotic plaque (AP) anatomy and composition, aiding in the identification of “vulnerable” plaques. In this context, hydrogel matrices, which have been demonstrated able to boost relaxometric properties of Gd-based contrast agents (CAs) by the effect of Hydrodenticity, represent a valuable tool towards the precision imaging of ASCVD improving the performance of this class of CAs while reducing systemic toxicity. In particular, hydrogel nanoparticles encapsulating Gd-DTPA can further contribute to providing CA-specific accumulation in the AP by nanoparticle surface decoration triggering an active targeting of the AP with the overall effect of allowing an earlier and more accurate diagnosis. In this work, we tested crosslinked Hyaluronic Acid Nanoparticles (cHANPs) in the complex environment of human atherosclerotic plaque. In addition, the surface of cHANPs was decorated with the antibody anti-CD36 (Ab36-cHANPs) for the active targeting of AP-associated macrophages. Results demonstrate that the Hydrodenticity of cHANPs and Ab36-cHANPs is preserved in this complex system and, preliminarily, that interaction of these probes with the AP is present.

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PEGylated Crosslinked Hyaluronic Acid Nanoparticles Designed Through a Microfluidic Platform for Nanomedicine

Abstract: The proposed microfluidic approach reveals its ability to overcome several limitations of the traditional processes and to become an easy-to-use platform for theranostic applications.

Cited by 16 publications

References 39 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

Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA

Targeting Nanostrategies for Imaging of Atherosclerosis

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