Elena Vismara

In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were engineered with an organic coating composed of low molecular weight heparin (LMWH) and bovine serum albumin (BSA), providing heparin-based nanoparticle systems (LMWH@SPIONs). The purpose was to merge the properties of the heparin skeleton and an inorganic core to build up a targeted theranostic nanosystem, which was eventually enhanced by loading a chemotherapeutic agent. Iron oxide cores were prepared via the co-precipitation of iron salts in an alkaline environment and oleic acid (OA) capping. Dopamine (DA) was covalently linked to BSA and LMWH by amide linkages via carbodiimide coupling. The following ligand exchange reaction between the DA-BSA/DA-LMWH and OA was conducted in a biphasic system composed of water and hexane, affording LMWH@SPIONs stabilized in water by polystyrene sulfonate (PSS). Their size and morphology were investigated via dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The LMWH@SPIONs’ cytotoxicity was tested, showing marginal or no toxicity for samples prepared with PSS at concentrations of 50 µg/mL. Their inhibitory activity on the heparanase enzyme was measured, showing an effective inhibition at concentrations comparable to G4000 (N-desulfo-N-acetyl heparin, a non-anticoagulant and antiheparanase heparin derivative; Roneparstat). The LMWH@SPION encapsulation of paclitaxel (PTX) enhanced the antitumor effect of this chemotherapeutic on breast cancer cells, likely due to an improved internalization of the nanoformulated drug with respect to the free molecule. Lastly, time-domain NMR (TD-NMR) experiments were conducted on LMWH@SPIONs obtaining relaxivity values within the same order of magnitude as currently used commercial contrast agents.

A significant portion of the world’s plastic is not properly disposed of and, through various processes, is degraded into microscopic particles termed micro- and nanoplastics. Marine and terrestrial faunae, including humans, inevitably get in contact and may inhale and ingest these microscopic plastics which can deposit throughout the body, potentially altering cellular and molecular functions in the nervous and other systems. For instance, at the cellular level, studies in animal models have shown that plastic particles can cross the blood–brain barrier and interact with neurons, and thus affect cognition. At the molecular level, plastics may specifically influence the folding of proteins, induce the formation of aberrant amyloid proteins, and therefore potentially trigger the development of systemic and local amyloidosis. In this review, we discuss the general issue of plastic micro- and nanoparticle generation, with a focus on their effects on protein folding, misfolding, and their possible clinical implications.

Cellulose derivatives have found significant applications in composite materials, mainly because of the increased mechanical performance they ensure. When added to cement-based materials, either in the form of nanocrystals, nanofibrils or micro/nanofibers, cellulose acts on the mixture with fresh and hardened properties, affecting rheology, shrinkage, hydration, and the resulting mechanical properties, microstructure, and durability. Commercial cotton wool was selected as starting material to produce multifunctional nanocelluloses to test as additives for mortars. Cotton wool was oxidized to oxidized nanocellulose (ONC), a charged nanocellulose capable of electrostatic interaction, merging cellulose and nanoparticles properties. Oxidized nanocellulose (ONC) was further functionalized by a radical-based mechanism with glycidyl methacrylate (GMA) and with a mixture of GMA and the crosslinking agent ethylene glycol dimethacrylate (EGDMA) affording ONC-GMA and ONC-GMA-EGDMA, both multifunctional-charged nanocellulose merging cellulose and bound acrylates properties. In this work, only ONC was found to be properly suitable for suspension and addition to a commercial mortar to assess the variation in mechanical properties and water-mortar interactions as a consequence of the modified microstructure obtained. The addition of oxidized nanocellulose caused an alteration of mortar porosity, with a decreased percentage of porosity and pore size distribution shifted towards smaller pores, with a consequent increase in compressive resistance, decrease in water absorption coefficient, and increased percentage of micropores present in the material, indicating a potential improvement in mortar durability.

Nanocellulose (NC) is getting ahead as a renewable, biodegradable and biocompatible biomaterial. The NCs for this study were recovered from industrial cotton waste (CFT) by acid hydrolysis (HNC) and by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) mediated oxidation (ONC). They were functionalized by radical based glycidyl methacrylate (GMA) grafting providing crystalline HNC-GMA and ONC-GMA, and by allylation (ALL) providing amorphous HNC-ALL and ONC-ALL. HNC, ONC and their derivatives were chemically and morphologically characterized. Crystalline NCs were found capable to adsorb, from diluted water solution (2 × 10⁻³ M), the antibiotics vancomycin (VC), ciprofloxacin (CP), amoxicillin (AM) and the disinfectant chlorhexidine (CHX), while amorphous NCs did not show any significant adsorption properties. Adsorption capability was quantified by measuring the concentration change in function of the contact time. The adsorption kinetics follow the pseudo-second order model and show complex adsorption mechanisms investigated by an intraparticle diffusion model and interpreted by structure-property relationships. ONC and ONC-GMA loaded with VC, and HNC and HNC-GMA loaded with CP were not colonized by Staphylococcus aureus and by Klebsiella pneumonia and suggested long lasting release capability. Our results can envisage developing CFT derived NCs for environmental applications (water remediation) and for biomedical applications (antibacterial NC). Among the future developments, it could also be of interest to take advantage of acidic, glycidyl and allyl groups’ reactivity to provide other NCs from the NC object of this study.

Among nanocelluloses, bacterial nanocellulose (BNC) has proven to be a promising candidate in a range of biomedical applications, from topical wound dressings to tissue-engineering scaffolds. Chemical modifications and incorporation of bioactive molecules have been obtained, further increasing the potential of BNC. This study describes the incorporation of vancomycin and ciprofloxacin in BNC and in modified BNC to afford bioactive BNCs suitable for topical wound dressings and tissue-engineering scaffolds. BNC was modified by grafting glycidylmethacrylate (GMA) and further cross-linking with ethylene glycol dimethacrylate (EGDMA) with the formation of stable C–C bonds through a radical Fenton-type process that involves generation of cellulose carbon centred radicals scavenged by methacrylate structures. The average molar substitution degree MS (MS = methacrylate residue per glucose unit, measured by Fourier transform infrared (FT–IR) analysis) can be modulated in a large range from 0.1 up to 3. BNC-GMA, BNC-EGDMA and BNC-GMA-EGDMA maintain the hydrogel status until MS reaches the value of 1. The mechanical stress resistance increase of BNC-GMA and BNC-GMA-EGDMA of MS around 0.8 with respect to BNC suggests that they can be preferred to BNC for tissue-engineering scaffolds in cases where the resistance plays a crucial role. BNC, BNC-GMA, BNC-EGDMA and BNC-GMA-EGDMA were loaded with vancomycin (VC) and ciprofloxacin (CP) and submitted to release experiments. BNC-GMA-EGDMA of high substitution degree (0.7–1) hold up to 50 percentage of the loaded vancomycin and ciprofloxacin amount, suggesting that they can be further investigated for long-term antimicrobial activity. Furthermore, they were not colonized by Staphylococcus aureus (S.A.) and Klebsiella pneumonia (K.P.). Grafting and cross-linking BNC modification emerges from our results as a good choice to improve the BNC potential in biomedical applications like topical wound dressings and tissue-engineering scaffolds.

Super paramagnetic iron oxide nanoparticles (SPION) were augmented by both hyaluronic acid (HA) and bovine serum albumin (BSA), each covalently conjugated to dopamine (DA) enabling their anchoring to the SPION. HA and BSA were found to simultaneously serve as stabilizing polymers of Fe₃O₄·DA-BSA/HA in water. Fe₃O₄·DA-BSA/HA efficiently entrapped and released the hydrophobic cytotoxic drug paclitaxel (PTX). The relative amount of HA and BSA modulates not only the total solubility but also the paramagnetic relaxation properties of the preparation. The entrapping of PTX did not influence the paramagnetic relaxation properties of Fe₃O₄·DA-BSA. Thus, by tuning the surface structure and loading, we can tune the theranostic properties of the system.

Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs–Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.

Heparin has been conjugated to Fe₃O₄, Co₃O₄, and NiO nanoparticles (NPs) through electrostatic interactions, producing colloidal suspensions of hybrid metal oxide heparin NPs that are stable in water. Negative zeta potentials and retention of heparin’s ability to capture toluidine blue indicate that heparin’s negative charges are exposed on the surface of the coated NPs. IR results confirmed the formation of nanohybrids as did NMR experiments, which were also interpreted on the basis of toluidine blue tests. Transmission electron microscopy results revealed that the heparin coating does not modify the shape or dimension of the NPs. Dynamic light scattering and negative zeta potential measurements confirmed that heparin surface functionalisation is an effective strategy to prevent NP aggregation.