Gianni Ciofani

• Ph.D.
• Senior Researcher at Istituto Italiano di Tecnologia

Tetragonal barium titanate nanoparticles (BTNPs) have been exploited as nanotransducers owing to their piezoelectric properties, in order to provide indirect electrical stimulation to SH-SY5Y neuron-like cells. Following application of ultrasounds to cells treated with BTNPs, fluorescence imaging of ion dynamics revealed that the synergic stimulati...

The investigation of the crossing of exogenous substances through the blood-brain barrier (BBB) is object of intensive research in biomedicine, and one of the main obstacles for reliable in vitro evaluations is represented by the difficulties at the base of developing realistic models of the barrier, which could resemble as most accurately as possi...

Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, represents the most aggressive primary brain tumor. The complex genetic heterogeneity, the acquired drug resistance, and the presence of the blood-brain barrier (BBB) limit the efficacy of the current therapies, with effectiveness demonstrated only in a small subset of patients. To...

Glioblastoma multiforme (GBM) is the deadliest brain tumor, characterized by an extreme genotypic and phenotypic variability, besides a high infiltrative nature in healthy tissues. Apart from very invasive surgical procedures, to date, there are no effective treatments, and life expectancy is very limited. In this work, an innovative therapeutic ap...

Glioblastoma multiforme (GBM) is a devastating tumor of the central nervous system, currently missing an effective treatment. The therapeutic gold standard consists of surgical resection followed by chemotherapy (usually with temozolomide, TMZ) and/or radio-therapy. TMZ does not, however, provide significant survival benefit after completion of tre...

The obtainment of innovative models recalling complex tumour architectures and activities in vitro is a challenging drive in the understanding of pathology molecular bases, yet it is a crucial path to the identification of targets for advanced oncotherapy. Cell environment recapitulation by 3D scaffolding and gravitational unloading of cell culture...

The regenerative capacity of the central nervous system (CNS) is limited. Understanding and enhancing the mechanisms that induce neural differentiation of neural stem cells (NSCs) is crucial for advancing regenerative medicine; one significant challenge in this effort is the remote delivery of pro‐differentiation cues. In this framework, a nanotech...

Laser‐Induced Graphene (LIG) is a 3D, conductive, porous material with a high surface area, produced by laser irradiation of synthetic polymers with high thermal stability. Recently, the focus has shifted toward sustainable bioderived and biodegradable precursors, such as lignocellulosic materials. Despite starch being an abundant and cost‐effectiv...

A significant challenge in the treatment of central nervous system (CNS) disorders is represented by the presence of the blood-brain barrier (BBB), a highly selective membrane that regulates molecular transport...

Glioblastoma (GBM) is a highly aggressive brain tumor known for its resistance to standard treatments. Despite surgery being a primary option, it often leads to incomplete removal and high recurrence rates. Photodynamic therapy (PDT) holds promise as an adjunctive treatment, but safety concerns and the need for high‐power lasers have limited its wi...

Polydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticl...

Oxidative stress is a widespread causative agent of disease. Together with its general relevance for biomedicine, such a dynamic is recognizably detrimental to space exploration. Among other solutions, cerium oxide nanoparticles (or nanoceria, NC) display a long-lasting, self-renewable antioxidant activity. In a previous experiment, we evaluated ox...

Most in vitro studies regarding new anticancer treatments are performed on 2D cultures, despite this approach imposes several limitations in recapitulating the real tumor behavior and in predicting the effects of therapy on both cancer and healthy tissues. Herein, advanced in vitro models based on scaffolds that support the 3D growth of glioma cell...

Microglia play a pivotal role in the central nervous system (CNS) homeostasis, acting as housekeepers and defenders of the surrounding environment. These cells can elicit their functions by shifting into two main phenotypes: pro‐inflammatory classical phenotype, M1, and anti‐inflammatory alternative phenotype, M2. Despite their pivotal role in CNS...

Brain drug delivery is severely hindered by the presence of the blood–brain barrier (BBB) . Its functionality relies on the interactions of the brain endothelial cells with additional cellular constituents, including pericytes, astrocytes, neurons, or microglia. To boost brain drug delivery, nanomedicines have been designed to exploit distinct deli...

Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, “Biology in Space and Analogue Environments”, focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present o...

Nano-sized piezoelectric materials allow for precise interaction with living systems to local deliver electrical cues. Recent innovations enhance their potential in tissue engineering and regenerative medicine.

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug‐resistant progression. GBM “builds” around its primary core a genetically heterogeneous tumor‐microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma‐associated microglia (GAM) represent...

Progress in mechanobiology allowed us to better understand the important role of mechanical forces in the regulation of biological processes. Space research in the field of life sciences clearly showed that gravity plays a crucial role in biological processes. The space environment offers the unique opportunity to carry out experiments without grav...

Smart nanomaterials, thanks to their stimuli-responsive properties, represent a promising class of nanostructures for biomedical applications. Their ability to undergo structural or functional changes in response to specific external cues has been exploited for the manipulation of cellular activities as a potential treatment for various health diso...

Microglial cells play a critical role in glioblastoma multiforme (GBM) progression, which is considered a highly malignant brain cancer. The activation of microglia can either promote or inhibit GBM growth depending on the stage of the tumor development and on the microenvironment conditions. The current treatments for GBM have limited efficacy; th...

The Research Topic "Insights in nanobiotechnology 2022/2023: novel developments, current challenges, and future perspectives" is an annual Research Topic featuring peer reviewed reviews, opinion papers, and research articles that looks to explore new insights, novel developments, current challenges, latest discoveries, recent advances, and future p...

The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: “How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?” This is one of the five major scientific issues of the ESA road...

Brain-on-a-chip (BoC) devices show typical characteristics of brain complexity, including the presence of different cell types, separation in different compartments, tissue-like three-dimensionality, and inclusion of the extracellular matrix components. Moreover, the incorporation of a vascular system mimicking the blood-brain barrier (BBB) makes B...

In recent years, the need for highly predictive brain cancer models to test new anticancer compounds and experimental therapeutic approaches has significantly increased. Realistic in vitro brain tumor-on-a-chip platforms would allow a more accurate selection of valid candidate drugs and nanomedicines, therefore alleviating the economic and ethical...

Ethosomes are novel lipid‐based vesicular systems that demonstrate unique improvements in drug delivery with respect to other nanoparticles, especially for transdermal applications. Their high ethanol content strongly improves flexibility and deformability, which allows squeezing through the intercellular spaces without any drug leakage. The ethano...

Prostate malignancy represents the second leading cause of cancer-specific death among the male population worldwide. Herein, enhanced intracellular magnetic fluid hyperthermia is applied in vitro to treat prostate cancer (PCa) cells with minimum invasiveness and toxicity and highly specific targeting. We designed and optimized novel shape-anisotro...

In recent years, a great deal of effort has been undertaken with regards to treatment of pathologies at the level of the central nervous system (CNS). Here, the presence of the blood-brain barrier (BBB) acts as a obstacle to the delivery of potentially effective drugs and makes accessibility to, and treatment of, the central nervous system one of t...

Stem cell-based therapies have shown promising results for the regeneration of the nervous system. However, the survival and integration of the stem cells in the neural circuitry is suboptimal and might compromise the therapeutic outcomes of this approach. The development of functional scaffolds capable of actively interacting with stem cells may o...

Under healthy physiological conditions, living organisms possess a variety of antioxidant mechanisms to scavenge overproduced reactive oxygen species (ROS). However, under pathological circumstances, endogenous antioxidant systems may not be adequate to eliminate the excessive amount of oxidants, and thus, a continuous exogenous antioxidant income...

The precise control of stem cell behavior, including differentiation, transdifferentiation, and reprogramming , is fundamental for safely and efficiently using human stem cells in regenerative medicine. Thanks to recent innovations and developments in the field of nanomedicine, as well as its integration with advanced molecular biology approaches,...

Upon coming into contact with the biological environment, nanostructures are immediately covered by biomolecules, particularly by proteins forming the so-called "protein corona" (PC). The phenomenon of PC formation has gained great attention in recent years due to its implication in the use of nanostructures in biomedicine. In fact, it has been sho...

Reactive oxygen species (ROS) are a common hallmark of many degenerative diseases, developing in all those cases where a failure of physiological antioxidant mechanisms occurs (in particular, antioxidant enzymes and the glutathione system), or in case of exposure to an extremely high level of oxidants. In this regard, antioxidant natural extracts a...

Natural antioxidants are a very large diversified family of molecules classified by activity (enzymatic or nonenzymatic), chemical-physical properties (e.g., hydrophilic or lipophilic), and chemical structure (e.g., vitamins, polyphenols, etc.). Research on natural antioxidants in various fields, such as pharmaceutics, nutraceutics, and cosmetics,...

Stimuli-responsive nanocarriers (SRN) hold great potential as drug delivery systems due to the ability to tune the release of the drugs by controlling the external stimuli. However, the synthesis of SRNs with layers of different functional polymers within their structure generally requires tedious processing steps involving surfactants. In this wor...

The combined approach of ex situ normothermic machine perfusion (NMP) and nanotechnology represents a strategy to mitigate ischemia/reperfusion injury in liver transplantation. We evaluated the uptake, distribution, and efficacy of antioxidant cerium oxide nanoparticles (nanoceria) during normothermic perfusion of discarded human livers. Nine disca...

Reactive oxygen species (ROS) are active molecules involved in several biological functions. When the production of ROS is not counterbalanced by the action of protective antioxidant mechanisms present in living...

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted attention in the biomedical field thanks to their ability to prompt hyperthermia in response to an alternated magnetic field. Hyperthermia is well known for inducing cell death, in particular in tumour cells, which seem to have a higher sensitivity to temperature increases. For this...

In the past decades, bone tissue engineering developed and exploited many typologies of bioreactors, which, besides providing proper culture conditions, aimed at integrating those bio‐physical stimulations that cells experience in vivo, to promote osteogenic differentiation. Nevertheless, the highly challenging combination and deployment of many st...

Accumulation of reactive oxygen species in cells leads to oxidative stress, with consequent damage for cellular components and activation of cell-death mechanisms. Oxidative stress is often associated with age-related conditions, as well as with several neurodegenerative diseases. For this reason, antioxidant molecules have attracted a lot of atten...

Glioblastoma multiforme (GBM) is one of the most common and aggressive brain tumors. It presents a very bad prognosis with a patients’ overall survival of 12-15 months; treatment failure is mainly ascribable to tumor recurrence. The development of a new tool, that could help the precise detection of the tumor border, is thus an urgent need. During...

Polydopamine (PDA) is a polymer that derives from the self-polymerization of the biomolecule dopamine. It can be easily synthesized to obtain spherical nanoparticles (PDNPs), tunable in terms of size, loaded cargo, and surface functionalization. PDNPs have been increasingly attracting the attention of the research community due to their elevated ve...

Angiogenesis plays a fundamental role in tumor development, as it is crucial for tumor progression, metastasis, and invasion. In this view, anti-angiogenic therapy has received considerable attention in several cancer types to inhibit tumor vascularization, and the progress of nanotechnology offers opportunities to target and release anti-angiogeni...

Smart materials able to respond to an external stimulus or an environmental condition represent milestone developments in modern medicine. Among them, zinc oxide (ZnO) is a highly intriguing inorganic material with versatile morphologies/shapes and multifunctional properties like piezoelectricity, enhanced reactive oxygen species (ROS) generation,...

Parkinson's disease (PD) is a progressive neurodegenerative disease with no satisfactory therapy options. Similar to other neurodegenerative conditions, such as Alzheimer's and Huntington's diseases, oxidative stress plays a key factor in the neurodegeneration process. To counteract the uncontrolled increase of reactive oxygen species (ROS) and oxi...

When nanostructures and other materials are exposed to biological fluids, they are immediately covered by a layer of biological molecules, which is typically referred to as a “biomolecular corona” (BC). This represents the first component of a material that interacts with biological systems, so characterizing the composition and the dynamic evoluti...

Electrical stimulation has shown great promise in biomedical applications, such as regenerative medicine, neuromodulation, and cancer treatment. Yet, the use of electrical end effectors such as electrodes requires connectors and batteries, which dramatically hamper the translation of electrical stimulation technologies in several scenarios. Piezoel...

Tetrapyrroles are the basis of essential physiological functions in most living organisms. These compounds represent the basic scaffold of porphyrins, chlorophylls, and bacteriochlorophylls, among others. Chlorophyll derivatives, obtained by the natural or artificial degradation of chlorophylls, present unique properties, holding great potential in...

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurological disease characterized by autosomal recessive mutations in the sacsin gene (SACS), that cause in patients progressive cerebellar atrophy, damage of the peripheral nerves, and cognitive impairment. No effective therapies have been proposed for ARSACS, even if some ev...

Gravity alterations elicit complex and mostly detrimental effects on biological systems. Among these, a prominent role is occupied by oxidative stress, with consequences for tissue homeostasis and development. Studies in altered gravity are relevant for both Earth and space biomedicine, but their implementation using whole organisms is often troubl...

Cancer metastasis is the major cause of cancer‐related morbidity and mortality. It represents one of the greatest challenges in cancer therapy, both because of the ability of metastatic cells to spread into different organs, and because of the consequent heterogeneity that characterizes primary and metastatic tumors. Nanomaterials can potentially b...

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response...

In vitro blood-brain barrier (BBB) models represent an efficient platform to conduct high-throughput quantitative investigations on BBB crossing ability of different drugs. Such models provide a closed system where different fundamental variables can be efficaciously tuned and monitored, and issues related to scarce accessibility of animal brains a...

Glioblastoma multiforme (GBM) is the most common and malignant neoplasia having origin in the brain. The current treatments involve surgery, radiotherapy, and chemotherapy, being the complete surgical resection the best option for the patient survival chances. However, in those cases where a complete removal is not possible, radiation and chemother...

Background Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for ext...

The modeling of the pathological microenvironment of the central nervous system (CNS) represents a disrupting approach for drug screening for advanced therapies against tumors and neuronal disorders. The in vitro investigations of the crossing and diffusion of drugs through the blood–brain barrier (BBB) are still not completely reliable, due to tec...

Oxidative stress is caused by the accumulation of reactive oxygen and nitrogen species (ROS and RNS) in the cellular microenvironment. These ROS and RNS damage important cell structures leading to cell apoptosis and senescence, thus causing a detrimental effect on numerous disease pathologies such as osteoarthritis, neurodegeneration and cardiovasc...

Oxidative stress represents a common issue in most neurological diseases, causing severe impairments of neuronal cell physiological activity that ultimately lead to neuron loss of function and cellular death. In this work, lipid-coated polydopamine nanoparticles (L-PDNPs) are proposed both as antioxidant and neuroprotective agents, and as well as a...

Glioblastoma multiforme is the most aggressive brain tumor due to its high invasiveness and genetic heterogeneity. Moreover, the blood-brain barrier prevents many drugs from reaching a therapeutic concentration at the tumor site, and most of the chemotherapeutics lacks in specificity towards cancer cells, accumulating in both healthy and diseased t...

Owing to the self-renewing reactive oxygen species (ROS) scavenger capability of cerium oxide nanoparticles (nanoceria), we tested in vivo radioprotective effects on stem cells and tissue regeneration using low-dose irradiated planarians as model system. We treated planarians with nanoceria or gum Arabic, as control, and we analyzed the expression...

Oxidative stress occurs when physiological antioxidant systems do not manage to counteract the excessive intracellular production of reactive oxygen species (ROS), which accumulate leading to irreversible oxidation of DNA and other biomacromolecules, and thus to the onset of pathological conditions. Autosomal recessive spastic ataxia of Charlevoix-...

Piezoelectric ceramic nanomaterials have recently attracted attention in the biomedical field thanks to their interesting electrical properties in response to mechanical stimulation (and vice versa) combined with a good biocompatibility and the ability to promote the regeneration of electrically sensitive tissues. In tissue engineering approaches,...

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain cancer, characterized by rapid progression, resistance to treatments, and low survival rates; the development of a targeted treatment for this disease is still today an unattained objective. Among the different strategies developed in the latest few years for the targeted de...

Cerebral ischemia (or ischemic stroke) is undeniably one of the most important life-threatening cerebral disorders. It occurs due to a clot formation in one of the blood arteries supplying the brain, causing a reduction or interruption of the blood flow. To date, the use of thrombolytics like the recombinant tissue plasminogen activator or the use...

Spheroids are 3D cellular systems largely adopted as model for high‐throughput screening of molecules and diagnostics tools. Furthermore, those cellular platforms also represent a model for testing new delivery carries for selective targeting. The coupling between the 3D cell environment and the nanovectors can be explored at the macroscale by opti...

Many central nervous system (CNS) diseases are still incurable and only symptomatic treatments are available. Oxidative stress is suggested to be a common hallmark, being able to cause and exacerbate the neuronal cell dysfunctions at the basis of these pathologies, such as mitochondrial impairments, accumulation of misfolded proteins, cell membrane...

Glioblastoma multiforme is the most common and aggressive malignant primary brain tumor. As implied by its name, the disease displays impressive intrinsic heterogeneity. Among other complications, inter‐ and intratumoral diversity hamper glioblastoma research and therapy, typically leaving patients with little hope for long‐term survival. Extensive...

Functional and stimuli-responsive nanofibers with an enhanced surface area/volume ratio provide controlled and triggered drug release with higher efficacy. In this study, chemotherapeutic agent Rose Bengal (RB) (4,5,6,7-tetrachloro-2′, 4′,5′,7′-tetraiodofluoresceindisodium)-loaded water-soluble polyvinyl alcohol (PVA) nanofibers were synthesized by...

Aiming at finding new solutions for fighting glioblastoma multiforme, one of most aggressive and lethal human cancer, here an in vitro validation of multifunctional nanovectors for drug delivery and hyperthermia therapy is proposed. Hybrid magnetic lipid nanoparticles have been fully characterized and tested on a multi-cellular complex model resemb...

Ischemic stroke is considered one of the most threatening neurological disorders with high percentages of mortality and morbidity worldwide. Although in recent years, several nanotechnological advances have improved the survival rates, severe untreated poststroke side‐effects continue to significantly influence the way of life of many. Tissue plasm...

In this study, hybrid nanocubes composed of magnetite (Fe3O4) and manganese dioxide (MnO2), coated with U‐251 MG cell‐derived membranes (CM‐NCubes) are synthesized. The CM‐NCubes demonstrate a concentration‐dependent oxygen generation (up to 15%), and, for the first time in the literature, an intracellular increase of temperature (6 °C) due to the...

Background: In most mammals, a vast array of genes coding for chemosensory receptors mediates olfaction. Odorant receptor (OR) genes generally constitute the largest multifamily (> 1100 intact members in the mouse). From the whole pool, each olfactory neuron expresses a single OR allele following poorly characterized mechanisms termed OR gene choi...

Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate criti...