Paolo Antonio Netti

University of Naples Federico II | UNINA · Department of Chemical, Materials and Industrial Production Engineering

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...

Citation: La Verde, G.; Sasso, A.; Rusciano, G.; Capaccio, A.; Fusco, S.; Mayol, L.; Biondi, M.; Silvestri, T.; Netti, P.A.; La Commara, M.; et al. Characterization of Hyaluronic Acid-Coated PLGA Nanoparticles by Surface-Enhanced Raman Spectroscopy. Int. Abstract: Nanoparticles (NPs) coated with hyaluronic acid (HA) seem to be increasingly promisin...

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...

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 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...

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...

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 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...

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 radio- therapies. Patients present, usually, pleural effusions which can be used for diagnostic purposes by cytological analysis. This effusion cytology may take w...

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...

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...

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...

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...

Engineered tissues featuring aligned ECM possess superior regenerative capabilities for the healing of damaged aligned tissues. The morphofunctional integration in the host's injury site improves if the aligned ECM elicits the unidirectional growth of vascular network. In this work we used a bottom-up tissue engineering strategy to produce endogeno...

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...

Often proteins association is a physiological process used by cells to regulate their growth and to adapt to different stress conditions, including mutations. In the case of a subtype of Acute Myeloid Leukemia (AML), mutations of nucleophosmin 1 (NPM1) protein cause its aberrant cytoplasmatic mislocalization (NPMc+). We recently pointed out an amyl...

Microneedle (MN) patches consisting of miniature needles have emerged as a promising tool to perforate the stratum corneum and translocate biomolecules into the dermis in a minimally invasive manner. Stimuli-responsive MN patches represent emerging drug delivery systems that release cargos on-demand as a response to internal or external triggers. I...

The intestinal microbiota is a real ecosystem composed of several bacterial species and a very huge amount of strains that through their metabolic activities play a crucial role in the development and performance of the immune system and other functions. Microbiota modulation by probiotics establishes a new era into the pharmaceutical and healthcar...

A new isoform of human manganese superoxide dismutase (SOD) has been recently isolated and obtained in a synthetic recombinant form and termed rMnSOD. As compared to other SODs, this isoform exhibits a dramatically improved cellular uptake and an intense antioxidant and antitumoral activity. Unfortunately, its use is severely hampered as this activ...

Porous microscaffolds (μ-scaffs) play a crucial role in modular tissue engineering as they control cell functions and guide hierarchical tissue formation toward building new functional tissue analogues. In the present study, we developed a new route to prepare porous polycaprolactone (PCL) μ-scaffs with a bioinspired trabecular structure that suppo...

The mechanical interpretation of the plethora of factors that governs cellular localization of amyloid aggregates is crucial for planning novel therapeutical interventions in neurodegenerative diseases since these aggregates exert a primary role in the proteostasis machinery. The uptake of Cell Penetrating Peptides (CPPs) conjugated with different...

Cell mechanical identity and substrate morphophysical and biochemical features are univocally linked through a complex relationship that is still largely unknown. Albeit the principles governing this relationship are not fully understood, some governing rules can be pragmatically derived from consolidated experimental evidence. In this chapter, som...

In this chapter, we present relevant results on how material signals, including distribution of ligands, topography, or stiffness, can affect the behavior of densely cell populated systems in which cell-cell interactions and matrix biosynthesis play a significant role in defining the behavior and functions of the system itself. Examples will be pro...

In the previous chapters, we illustrated and discussed how material characteristics, both chemical and physical, affect cell functions and fate through the adhesion-cytoskeleton-nucleus axis. The analysis, however, is centered on static substrates, i.e., materials whose features do not change significantly in time and space. Yet, the native environ...

Cell adhesion on material surfaces is fundamentally an interface problem. What is behind this interface is a complex network of structural and signaling molecules that profoundly regulate and guide cell behavior. Cells possess very refined mechanisms to recognize and react to microenvironmental features. Understanding how these mechanisms work may...

Cells live in an environment that is biochemical and biophysical in nature, whose characteristics dictate cells’ functions and fate. While a consolidated literature on the influence of soluble biomolecules on cell behavior exists, the effects of biophysical entities are comparatively less understood. In fact, cells are able to perceive the microarc...

The majority of cells in our body are adhesion-dependent, which means that their functions are affected by the characteristic of the extracellular support on which they adhere. Transmembrane receptors and a myriad of intracellular proteins are committed to establish adhesion and to mechanically coupling the cell to the environment. However, complex...

The microfluidic based characterization (static light scattering) of morphometric and optical cell properties over time related to an in-flow applied compressive force over time can reveal useful insides in cell-mechanical processes.

Modeling flow field in tumor regions interstitial space is of primary importance, because of the importance of advection in macromolecule drug delivery. Its deformation has also to be taken into account because of the forces caused by the fluid; if the tumor region is not isothermal, this deformation can be also strongly affected by temperature fie...

Cell mechanical properties are powerful biomarkers for label-free phenotyping. To date, microfluidic approaches assay mechanical properties by measuring changes in cellular shape, applying extensional or shear flows or forcing cells to pass through constrictions. In general, such approaches use high-speed imaging or transit time measurements to eva...

Exosomes are phospholipid-based particles endogenously produced by both normal and tumor cells. Initially identified as a pathway for shuttling cellular waste, for a long time they were thought to act as “garbage bags”, and only in the past few years have they emerged as a promising drug delivery system. In this review, we provide an overview of th...

A large body of literature has demonstrated that the mechanical properties of microenvironment have a key role in regulating cancer cell adhesion, motility, and invasion. In this work, we have introduced two additional parameters, named cell trajectory extension and area traveled by cell, to describe the tendency of normal tissue and metastatic can...

Transdermal microneedle patches have attracted significant attention in the medical arena over the last decade as alternatives to traditional drug delivery methods. Microneedle patches are capable of delivering their payloads using burst‐ and sustained‐release mechanisms, or in response to internal/external triggers, to optimize their therapeutic p...

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 path...

Anisotropic gold nanoparticles displaying plasmon band in the near infrared region can play a crucial role in cancer therapy particularly with techniques such as photothermal therapy (PTT) and photodynamic therapy (PDT). Herein, we report an efficient, sustainable, one pot protocol for the fabrication of an unusual gold anisotropic shape, which we...

Surface topography is a key parameter in regulating the morphology and behavior of single cells. At multicellular level, coordinated cell displacements drive many biological events such as embryonic morphogenesis. However, the effect of surface topography on collective migration of epithelium has not been studied in detail. Mastering the connection...

Here, we proposed an innovative organotypic cervical tumor model able to investigate the bi-directional crosstalk between epithelium and stroma as well as the key disease features of the epithelial-mesenchymal transition (EMT) process in vitro. By using a modular tissue assembling approach, we developed 3D cervical stromal models composed of primar...

Macromolecules and drug delivery to solid tumours is strongly influenced by fluid flow through interstitium, and pressure-induced tissue deformations can have a role in this. Recently, it has been shown that temperature-induced tissue deformation can influence interstitial fluid velocity and pressure fields, too. In this paper, the effect of modula...

Introduction: CoenzymeQ10 (CoQ10) is a well-known antioxidant and anti-inflammatory agent with cardioprotective properties. However, clinical trials based on its oral administration have failed to provide significant effect on cardiac functionality. The main limitation of CoQ10 is based on its very low oral bioavailability and instability that lim...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Featured Application: In this study two extraction methods for Ganoderma lucidum spores were evaluated for the potential use of extracted compounds in cancer treatments. Our findings showed that the innovative Rapid Solid Liquid Dynamic Extraction (RSLDE) permits the successful extraction of compounds with antiproliferative activity against human c...

Cystic fibrosis is characterized by lung dysfunction involving mucus hypersecretion, bacterial infections, and inflammatory response. Inflammation triggers pro-fibrotic signals that compromise lung structure and function. At present, several in vitro cystic fibrosis models have been developed to study epithelial dysfunction but none of these focuse...

The structural and mechanical properties of the microenvironmental context have a profound impact on cancer cell motility, tumor invasion, and metastasis formation. In fact, cells react to their mechanical environment modulating their adhesion, cytoskeleton organization, changes of shape, and, consequently, the dynamics of their motility. In order...

Despite the well-known role of chronic human papillomavirus (HPV) infections in causing tumors (i.e., all cervical cancers and other human malignancies from the mucosal squamous epithelia, including anogenital and oropharyngeal cavity), its persistence is not sufficient for cancer development. Other co-factors contribute to the carcinogenesis proce...

Escherichia coli filamentous bacteriophages (M13, f1, or fd) have attracted tremendous attention from vaccinologists as a promising immunogenic carrier and vaccine delivery vehicle with vast possible applications in the development of vaccines. The use of fd bacteriophage as an antigen delivery system is based on a modification of bacteriophage dis...

In recent years, drug delivery systems have become some of the main topics within the biomedical field. In this scenario, polymeric microparticles (MPs) are often used as carriers to improve drug stability and drug pharmacokinetics in agreement with this kind of treatment. To avoid a mere and time-consuming empirical approach for the optimization o...

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 tow...

The extracellular microenvironment proved to exert a potent regulatory effect over different aspects of Embryonic Stem Cells (ESCs) behavior. In particular, the employment of engineered culture surfaces aimed at modulating ESC self-organization resulted effective in directing ESCs toward specific fate decision. ESCs fluctuate among different levels...

Intestine-Liver-on-chip systems can be useful to predict oral drug administration and first-pass metabolism in vitro in order to partly replace the animal model. While organ-on-chip technology can count on sophisticated micro-physiological devices, the engineered organs still remain artificial surrogates of the native counterparts. Here, we used a...

The investigation of conformational features of regions of amyloidogenic proteins are of great interest to deepen the structural changes and consequent self-aggregation mechanisms at the basis of many neurodegenerative diseases. Here we explore the effect of β-hairpin inducing motifs on regions of prion protein covering strands S1 and S2. In detail...

The growing demand for patient-compliance therapies in recent years has led to the development of transdermal drug delivery, which possesses several advantages compared with conventional methods. Delivering protein through the skin by transdermal patches is extremely difficult due to the presence of the stratum corneum which restricts the applicati...

Collagen is the main component of the extracellular matrix and it plays a key role in tumor progression. Commercial collagen solutions are derived from animals, such as rat-tail and bovine or porcine skin. Their cost is quite high and the product is stable only at low temperature, with the disadvantage of a short expiring date. Most importantly, lo...

The aim of this chapter is to expound on the methods for the development of a synthetic analog of the extracellular matrix (ECM) that, because of a careful choice of its characteristics, can regulate cell behavior and tissue progression for applications in neural regenerative medicine. Neural cells—neurons—are the smallest building blocks of the ce...

The development of integrated positron emission tomography (PET)/ magnetic resonance imaging (MRI) scanners opened a new scenario for cancer diagnosis, treatment, and follow-up. Multimodal imaging combines functional and morphological information from different modalities, which, singularly, cannot provide a comprehensive pathophysiological overvie...

Local curvatures on the cell membrane serve as signaling hubs that promote curvature-dependent protein interactions and modulate a variety of cellular processes including endocytosis, exocytosis, and the actin cytoskeleton. However, precisely controlling the location and the degree of membrane curvature in live cells has not been possible until rec...

The formation of severe scars still represents the result of the closure process of extended and deep skin wounds. To address this issue, different bioengineered skin substitutes have been developed but a general consensus regarding their effectiveness has not been achieved yet. It will be shown that bioengineered skin substitutes, although represe...

In tissue engineering, the use of supercritical CO2 foaming is a valuable and widespread choice to design and fabricate porous bioactive scaffolds for cells culture and new tissue formation in three dimensions. Nevertheless, the control of scaffold pores size, shape and spatial distribution with foaming technique remains, to date, a critical limiti...