Paolo Antonio Netti

• phd
• Professor (Full) at University of Naples Federico II

Herein, the effects of a novel half-sandwich Os(II) complex on the aggregation of an amyloid model system, derived from the C-terminal domain of the nucleophosmin 1 protein (NPM1264–277), were investigated. The thioflavin T (ThT) binding assay revealed that the complex [(η⁶-toluene)Os(NHCglu)Cl2] (where NHCglu is the N-heterocyclic carbene ligand 1...

Intrinsic biophysical and morphological features are essential for the label-free identification of different cell types. Indeed, apart from object size, density could represent a key parameter for single-cell analysis. However, the measurement of such a parameter is challenging. Therefore, we present a straightforward and versatile microfluidic ch...

Carbon nanomaterials have been widely applied for cutting edge therapeutic applications as they offer tunable physio-chemical properties with economic scale-up options. Nuclear delivery of cancer drugs has been of prime focus since it controls important cellular signaling functions leading to greater anti-cancer drug efficacies. Better cellular dru...

Magnetic hyperthermia (MHT) is a promising cancer treatment that exploits the heating capabilities of magnetic nanoparticles (MNPs) when exposed to alternating magnetic fields. The primary challenge in optimizing MHT lies in understanding the influence of MNP distribution within the tumor microenvironment. This study presents realistic simulations...

The stiffness of the extracellular matrix plays a crucial role in cell motility and spreading, influencing cell morphology through cytoskeleton organization and transmembrane proteins’ expression. In this context, mechanical characterization of both cells and the extracellular matrix gains prominence for enhanced diagnostics and clinical decision-m...

There is a growing interest in the search for metal-based therapeutics for protein misfolding disorders such as Alzheimer’s disease (AD). A novel and largely unexplored class of metallodrugs is constituted by paddlewheel diruthenium complexes, which exhibit unusual water solubility and stability and unique coordination modes to proteins. Here, we i...

Multicellular organisms exhibit synergistic effects among their components, giving rise to emergent properties crucial for their genesis and overall functionality and survival. Morphogenesis involves and relies upon intricate and biunivocal interactions among cells and their environment, that is, the extracellular matrix (ECM). Cells secrete their...

Soft microrobots have gained great attention in the bioengineering field due to their ability to navigate into biological fluids, overcoming biological barriers. Indeed, thanks to the size and controlled movement they can easily de-liver drugs to a specific target. In this work, we present completely natural and biodegradable propulsion soft micro-...

The advent of 3D bioprinting technologies in tissue engineering has unlocked the potential to fabricate in vitro tissue models, overcoming the constraints associated with the shape limitations of preformed scaffolds. However, achieving an accurate mimicry of complex tissue microenvironments, encompassing cellular and biochemical components, and orc...

Mammalian sperm motility is getting more relevant due to rising infertility rates worldwide, generating the need to improve conventional analysis and diagnostic approaches. Nowadays, computer assisted sperm analysis (CASA) technologies represent a popular alternative to manual examination which is generally performed by observing sperm motility in...

Tissue-engineered skin substitutes are promising tools to cover large and deep skin defects. However, the lack of a synergic and fast regeneration of the vascular network, nerves, and skin appendages limits complete skin healing and impairs functional recovery. It has been highlighted that an ideal skin substitute should mimic the structure of the...

The biological effects of ionizing radiation are exploited in the clinical practice of radiotherapy to destroy tumour cells while sparing the surrounding normal tissue. While most of the radiotherapy research focused on DNA damage and repair, recently a great attention is going to cells' interactions with the mechanical microenvironment of both mal...

The physical and chemical properties of paddlewheel diruthenium compounds are highly dependent on the nature of the ligands surrounding the bimetallic core. Herein, we compare the ability of two diruthenium compounds, [Ru2Cl(D-p-FPhF)(O2CCH3)3]·H2O (1) (D-p-FPhF– = N,N′-bis(4-fluorophenyl)formamidinate) and K3[Ru2(O2CO)4]·3H2O (2), to act as inhibi...

Neural network-based image classification is widely used in life science applications. However, it is essential to extrapolate a correct classification method for unknown images, where no prior knowledge can be utilised. Under a closed set assumption, unknown images will be inevitably misclassified, but this can be genuinely overcome choosing an op...

Exposure to metal nanoparticles is potentially harmful, particularly when occurring during embryogenesis. In this study, we tested the effects of commercial AuNPs and AgNPs, widely used in many fields for their features, on the early development of Xenopus laevis, an anuran amphibian key model species in toxicity testing. Through the Frog Embryo Te...

The engineering of nanoparticles impacts the control of their nano-bio interactions at each level of the delivery pathway. Therefore, optimal nanoparticle physicochemical properties should be identified to favour on-target interactions and deliver efficiently active compounds to a specific target. To date, traditional batch processes do not guarant...

A computational 3D analysis of liposomal drug delivery to investigate the effectiveness of this innovative therapy as an alternative to conventional chemotherapy is shown in this study. The temperature field evolution is obtained via the Local Thermal Non-Equilibrium (LTNE) bioheat model by including both variable porosity and blood vessels sizes t...

To improve the efficacy of nanoparticles (NPs) and boost their theragnostic potential for brain diseases, it is key to understand the mechanisms controlling blood–brain barrier (BBB) crossing. Here, the capability of 100 nm carboxylated polystyrene NPs, used as a nanoprobe model, to cross the human brain endothelial hCMEC/D3 cell layer, as well as...

The extracellular microenvironment regulates cell decisions through the accurate presentation at the cell surface of a complex array of biochemical and biophysical signals that are mediated by the structure and composition of the extracellular matrix (ECM). On the one hand, the cells actively remodel the ECM, which on the other hand affects cell fu...

Novel microparticles have generated growing interest in diagnostics for potential sensitivity and specificity in biomolecule detection and for the possibility to be integrated in a micro-system array as a lab-on-chip. Indeed, bead-based technologies integrated in microfluidics could speed up incubation steps, reduce reagent consumption and improve...

In this work, we compare the role of two different uptake mechanisms in the effectiveness of a nanoformulated drug, specifically insulin. Insulin is activated by interacting with insulin receptors exposed on the liver cell membrane that triggers the uptake and storage of glucose. To prove that the uptake mechanism of a delivery system can interfere...

Cystic fibrosis (CF) is one of the most frequent genetic diseases, caused by dysfunction of the CF transmembrane conductance regulator (CFTR) chloride channel. CF particularly affects the epithelium of the respiratory system. Therapies aim at rescuing CFTR defects in the epithelium, but CF genetic heterogeneity hinders the finding of a single and g...

Current 3D cancer models (in vitro) fail to reproduce complex cancer cell extracellular matrices (ECMs) and the interrelationships occurring (in vivo) in the tumor microenvironment (TME). Herein, we propose 3D in vitro colorectal cancer microtissues (3D CRC μTs), which reproduce the TME more faithfully in vitro. Normal human fibroblasts were seeded...

Phosphatidylinositol-5-phosphate (PtdIns5P)−4-kinases (PIP4Ks) are stress-regulated phosphoinositide kinases able to phosphorylate PtdIns5P to PtdIns(4,5)P2. In cancer patients their expression is typically associated with bad prognosis. Among the three PIP4K isoforms expressed in mammalian cells, PIP4K2B is the one with more prominent nuclear loca...

Objective: In this context, our study aimed to ascertain whether the esterification of 24-hydroxycholesterol, a process heavily affected by oxidative stress, is altered in ALS. Methods: The study examined the level of 24-hydroxycholesteryl esters in cerebrospinal fluid and plasma of 18 ALS patients by spectroscopic technique as Ultra-high perfor...

Low abundance, small size, and sequence similarities render microRNA (miRNAs) detection challenging, particularly in real samples, where quantifying weakly expressed miRNAs can be arduous due to interference of more abundant molecules. The standard quantitative reverse transcription polymerase chain reaction (qRT-PCR) requires multiple steps, therm...

Tissue engineering needs bioactive drug delivery scaffolds capable of guiding cell biosynthesis and tissue morphogenesis in three dimensions. Several strategies have been developed to design and fabricate ECM-mimicking scaffolds suitable for directing in vitro cell/scaffold interaction, and controlling tissue morphogenesis in vivo. Among these stra...

Unlabelled: Bacteriophages have attracted great attention in the bioengineering field in diverse research areas from tissue engineering to therapeutic and clinical applications. Recombinant filamentous bacteriophage, carrying multiple copies of foreign peptides on protein capsid has been successfully used in the vaccine delivery setting, even if t...

Nanoparticles (NPs) coated with hyaluronic acid (HA) seem to be increasingly promising for targeted therapy due to HA chemical versatility, which allows them to bind drugs of different natures, and their affinity with the transmembrane receptor CD-44, overexpressed in tumor cells. However, an essential aspect for clinical use of NPs is formulation...

Mechanobiology aims at disclosing the functions and mechanisms by which mechanical, and architectural signals of the tissue microenvironment, control cell behaviors and cell states. Alteration in cellular mechanoperception and responsiveness is now recognized at the roots of cancer, and this is particularly well-appreciated in the context of lung a...

Cell deformability is a well-established marker of multiple cell states for phenotyping and classification purposes. However, the measurement of rheological/mechanical cell properties is often hindered by complex measurement systems and long experimental times. Here, we present a microfluidic approach, as a simple tool to rapidly deform cells in a...

The establishment of novel disruptive technologies represents a common requirement for the sustainable development as reported in the 2030 agenda established by United Nations. As demonstrated by the Covid-19 pandemic, and furtherly highlighted by the current global challenges, i.e. precision agriculture, decentralized testing, personalized medicin...

Carbon nanomaterials are an inventive class of materials with wide applications in state-of-the-art bioimaging and therapeutics. They allow a broad range of tunable and integrated advantages of structural flexibility, chemical and thermal stability, upright electrical conductivity, and the option of scale-up and mass production. In the context of n...

Cell deformability is a well-established marker of cell states for diagnostic purposes. However, the measurement of a wide range of different deformability levels is still challenging, especially in cancer, where a large heterogeneity of rheological/mechanical properties is present. Therefore, a simple, versatile and cost-effective recognition meth...

Malignant cells grow in a complex microenvironment that plays a key role in cancer progression. The "dynamic reciprocity" existing between cancer cells and their microenvironment is involved in cancer differentiation, proliferation, invasion, metastasis, and drug response. Therefore, understanding the molecular mechanisms underlying the crosstalk b...

Supramolecular assemblies of short peptides are experiencing a stimulating flowering. Herein, we report a novel class of bioinspired pentapeptides, not bearing Phe, that form hydrogels with fibrillar structures. The inherent sequence comes from the fragment 269-273 of Nucleophosmin 1 protein, that is normally involved in liquid–liquid phase separat...

The demand for artificial or bioartificial engineered tissues is increasing today in regenerative medicine techniques to replace and restore the physiological function of damaged tissues. Such engineered constructs hold different properties depending on the tissue to be replicated. As for vascularized tissues, complex biocompatible structures, name...

Pro-inflammatory (M1) and anti-inflammatory (M2) macrophage phenotypes play a fundamental role in the immune response. The interplay and consequently the classification between these two functional subtypes is significant for many therapeutic applications. Albeit, a fast classification of macrophage phenotypes is challenging. For instance, image-ba...

The microenvironment of breast cancer actively participates in tumorigenesis and cancer progression. The changes observed in the architecture of the extracellular matrix initiate an oncogene-mediated cell reprogramming, that leads to a massive triggering of YAP nuclear entry, and, therefore, to cancer cell proliferation, invasion and probably to in...

Modular tissue engineering (mTE) strategies aim to build three-dimensional tissue analogues in vitro by the sapient combination of cells, micro-scaffolds (μ-scaffs) and bioreactors. The translation of these newly engineered tissues into current clinical approaches is, among other things, dependent on implant-to-host microvasculature integration, a...

Among oral delivery systems, oil in water nano-emulsions (O/W NEs) are of particular interest to improve pharmacokinetics of lipophilic compounds. Recently, we have implemented a successful strategy to improve O/W NEs stability, based on a polymeric coating on an oil core, namely secondary O/W NEs, through the use of pharma grade formulations. Howe...

Stem cell shape and mechanical properties in vitro can be directed by geometrically defined micropatterned adhesion substrates. However, conventional methods are limited by the fixed micropattern design, which cannot recapitulate the dynamic changes of the natural cell microenvironment. Current methods to fabricate dynamic platforms usually rely on...

Mechanical forces, acting on eukaryotic cells, are responsible for cell shape, cell proliferation, cell polarity, and cell differentiation thanks to two cells abilities known as mechanosensing and mechanotransduction. Mechanosensing consists of the ability of a cell to sensemechanical cues,whilemechanotransduction is the capacity of a cell to respo...

In the past decade, modular scaffolds prepared by assembling biocompatible and biodegradable building blocks (e.g. microspheres) have found promising applications in tissue engineering (TE) towards the repair/regeneration of damaged and impaired tissues. Nevertheless, to date this approach has failed to be transferred to the clinic due to technolog...

The preparation of gold nanoparticles with multimodal properties such as near-infrared absorption, high surface-enhanced Raman scattering, cell internalization and low cytotoxicity is a challenging task. In this study, we developed a sustainable protocol to develop gold nanoparticles, using trisodium citrate as reducing, stabilizing, and shape-modu...

The healing of deep skin wounds is a complex phenomenon evolving according with a fine spatiotemporal regulation of different biological events (hemostasis, inflammation, proliferation, remodeling). Due to the spontaneous evolution of damaged human dermis toward a fibrotic scar, the treatment of deep wounds still represents a clinical concern. Bioe...

Here, we propose an immune-responsive human Microbiota-Intestine axis on-chip as a platform able to reproduce the architecture and vertical topography of the microbiota with a complex extracellular microenvironment consisting of a responsive extra cellular matrix (ECM) and a plethora of immune-modulatory mediators released from different cell popul...

The cell nucleus plays a critical role in mechanosensing and mechanotransduc-tion processes, by adaptive changes of its envelope composition to external biophysical stimuli such as substrate rigidity and tensile forces. Current measurement approaches lack precise control in stress application on nuclei, thus significantly impairing a complete mecha...

Phosphatidylinositol-5-phosphate (PtdIns5P)-4-kinases (PIP4Ks) are stress-regulated phosphoinositide kinases able to phosphorylate PtdIns5P to PtdIns(4,5)P2. In cancer patients their expression is typically associated with bad prognosis. Among the three PIP4K isoforms expressed in mammalian cells, PIP4K2B is the one with more prominent nuclear loca...

Bacterial cellulose (BC) is a highly pure form of cellulose produced by bacteria, which possesses numerous advantages such as good mechanical properties, high chemical flexibility, and the ability to assemble in nanostructures. Thanks to these features, it achieved a key role in the biomedical field and in drug delivery applications. BC showed its...

In the last decade, PEG-based hydrogels have been extensively used for the production of microparticles for biosensing applications. The biomolecule accessibility and mass transport rate represent key parameters for the realization of sensitive microparticles, therefore porous materials have been developed, mainly resorting to the use of inert poro...

In cancer therapy, stimulus-responsive drug delivery systems are of particular interest for reducing side effects in healthy tissues and improving drug selectivity in the tumoral ones. Here, a strategy for the preparation of a photo-responsive cross-linked trilayer deposited onto an oil-in-water nanoemulsion via a layer-by-layer technique is report...

Malignant pleural mesothelioma is a relatively rare, but devastating tumor, because of the difficulties in providing early diagnosis and effective treatments with conventional chemo- and radiotherapies. Patients usually present pleural effusions that can be used for diagnostic purposes by cytological analysis. This effusion cytology may take weeks...

An optimal design of nanocarriers is required to overcome the gap between synthetic and biological identity, improving the clinical translation of nanomedicine. A new generation of hybrid vehicles based on lipid–polymer coupling, obtained by Microfluidics, is proposed and validated for theranostics and multimodal imaging applications. A coupled Hyd...

Organ on chip (OOC) has emerged as a major technological breakthrough and distinct model system revolutionizing biomedical research and drug discovery by recapitulating the crucial structural and functional complexity of human organs in vitro. OOC are rapidly emerging as powerful tools for oncology research. Indeed, Cancer on chip (COC) can ideally...

The recent advancements in hybrid positron emission tomography–magnetic resonance imaging systems (PET/MRI) have brought massive value in the investigation of disease processes, in the development of novel treatments, in the monitoring of both therapy response and disease progression, and, not least, in the introduction of new multidisciplinary mol...

The exposure of organisms to the nanoparticulate is potentially hazardous, particularly when it occurs during embryogenesis. The effects of commercial SiO2NPs in early development were studied, using Xenopus laevis as a model to investigate their possible future employment by means of the Frog Embryo Teratogenesis Assay-Xenopus test (FETAX). The Si...

In spite of tremendous advances made in the comprehension of mechanotransduction, implementation of mechanobiology assays remains challenging for the broad community of cell biologists. Hydrogel substrates with tunable stiffness are essential tool in mechanobiology, allowing to investigate the effects of mechanical signals on cell behavior. A bottl...

Herein we describe the development of a mix-read bioassay based on a three-dimensional (3D) poly ethylene glycol—(PEG)-hydrogel microparticles for the detection of oligonucleotides in complex media. The key steps of hydrogels synthesis and molecular recognition in a 3D polymer network are elucidated. The design of the DNA probes and their density i...

Microfluidics is emerging as a promising tool to control physicochemical properties of nanoparticles and to accelerate clinical translation. Indeed, microfluidic-based techniques offer more advantages in nanomedicine over batch processes, allowing fine-tuning of process parameters. In particular, the use of microfluidics to produce nanoparticles ha...

Background: To date, in personalized medicine approaches, single-cell analyses such as circulating tumour cells (CTC) are able to reveal small structural cell modifications, and therefore can retrieve several biophysical cell properties, such as the cell dimension, the dimensional relationship between the nucleus and the cytoplasm and the optical d...

Natural killer (NK) cells are indicated as favorite candidates for innovative therapeutic treatment and are divided into two subclasses: immature regulatory NK CD56bright and mature cytotoxic NK CD56dim. Therefore, the ability to discriminate CD56dim from CD56bright could be very useful because of their higher cytotoxicity. Nowadays, NK cell classi...

In recent decades, endogenous nanocarrier-exosomes have received considerable scientific interest as drug delivery systems. The unique proteo-lipid architecture allows the crossing of various natural barriers and protects exosomes cargo from degradation in the bloodstream. However, the presence of this bilayer membrane as well as their endogenous c...

The cytoskeleton is involved in several biological processes, including adhesion, motility, and intracellular transport. Alterations in the cytoskeletal components (actin filaments, intermediate filaments, and microtubules) are strictly correlated to several diseases, such as cancer. Furthermore, alterations in the cytoskeletal structure can lead t...

Protein aggregation is suggested as a reversible, wide-spread physiological process used by cells to regulate their growth and adapt to different stress conditions. Nucleophosmin 1(NPM1) protein is an abundant multifunctional nucleolar chaperone and its gene is the most frequently mutated in Acute Myeloid Leukemia (AML) patients. So far, the role o...

Selectivity in tumor targeting is one of the major issues in cancer treatment. Therefore, surface functionalization of drug delivery systems with active moieties, able to selectively target tumors, has become a worldwide-recognized strategy. The CD44 receptor is largely used as a biomarker, being overexpressed in several tumors, and consequently as...

Recently, we developed ultra-stable oil in water nano-emulsions (O/W NEs), able to carry both internal and external cargos (Somes), such as lipophilic compounds and hydrophilic coatings, respectively, that we call here NEsoSomes. O/W NEs are an excellent bioengineering tool for drug and molecules delivery, due to their ability to dissolve a large n...

The control of the three-dimensional (3D) polymer network structure is important for permselective materials when specific biomolecule detection is needed. Here we investigate conditions to obtain a tailored hydrogel network that combines both molecular filtering and molecular capture capabilities for biosensing applications. Along this line, short...

In the last decade, additive manufacturing (AM) processes have updated the fields of biomaterials science and drug delivery as they promise to realize bioengineered multifunctional devices and implantable tissue engineering (TE) scaffolds virtually designed by using computer-aided design (CAD) models. However, the current technological gap between...

The development of assays for protein biomarkers in complex matrices is a demanding task that still needs implementation of new approaches. Antibodies as capture agents have been largely used in bioassays but their low stability, low-efficiency production, and cross-reactivity in multiplex approaches impairs their larger applications. Instead, synt...

Highly cross-linked polyethylene glycol monoliths (HCPEG) with interconnected micro and nanoporosity are produced via photo-crosslinking of low internal phase emulsions (LIPE). Unlike previous works, this approach allows the pre-processing functionalization of both polymer matrix and porosity by loading both phases of the emulsion template with sev...