Search

Carbon nanomaterials (CNMs) are an incredibly versatile class of materials that can be used as scaffolds to construct anticancer nanocarrier systems. The ease of chemical functionalisation, biocompatibility, and intrinsic therapeutic capabilities of many of these nanoparticles can be leveraged to design effective anticancer systems. This article is the first comprehensive review of CNM-based nanocarrier systems that incorporate approved chemotherapy drugs, and many different types of CNMs and chemotherapy agents are discussed. Almost 200 examples of these nanocarrier systems have been analysed and compiled into a database. The entries are organised by anticancer drug type, and the composition, drug loading/release metrics, and experimental results from these systems have been compiled. Our analysis reveals graphene, and particularly graphene oxide (GO), as the most frequently employed CNM, with carbon nanotubes and carbon dots following in popularity. Moreover, the database encompasses various chemotherapeutic agents, with antimicrotubule agents being the most common payload due to their compatibility with CNM surfaces. The benefits of the identified systems are discussed, and the factors affecting their efficacy are detailed.

Cancer is a globally prevalent cause of premature mortality. Of growing interest is the development of novel anticancer therapies and the optimisation of associated risks. Major issues presently facing conventional anticancer therapies include systemic toxicity, poor solubility, membrane permeability, and multidrug resistance Nanocarriers have been employed to address these issues. Nanocarriers encapsulate anticancer drugs, enabling them to bypass biological barriers and minimise their adverse side effects. These drug delivery systems offer extensive benefits as they can be modified to gravitate towards specific environmental conditions. To further enhance the safety and efficacy of these drug carriers, modern developments have included incorporating a molecular switching mechanism into their structure. These molecular switches are responsive to endogenous and exogenous stimuli and may undergo reversible and repeatable conformational changes when activated. The incorporation of molecular switches can, therefore, impart stimuli-responsive drug-release control on a DDS. These stimuli can then be manipulated to offer precise dosage control over the drug release at a specific target site. This review discusses recent developments in the design of DDSs incorporating light and pH-responsive molecular switches as drug release controllers.

Nanocomposite hydrogels have attracted researchers’ attention in recent years to achieve superior performances in a variety of materials applications. In this work, we describe the outcome of three different strategies to combine a self-assembling tripeptide and carbon nano-onions (CNOs), through covalent and non-covalent approaches, into supramolecular and nanostructured hydrogels. Importantly, the tripeptide coated the nano-onions and extended their aqueous dispersions’ stability by several hours. Furthermore, CNOs could be loaded in the tripeptide hydrogels at the highest level ever reported for nanocarbons, indicating high compatibility between the components. The materials were formed in phosphate-buffered solutions, thus paving the way for biological applications, and were characterized by several spectroscopic, microscopic, thermogravimetric, and rheological techniques. In vitro experiments demonstrated excellent cytocompatibility.

Boron/nitrogen co-doped carbon nano-onions (BN-CNOs) are spherical nanoparticles that consist of multiple inter-nestled fullerene layers, giving them an onion-like internal structure. They have potential as nanocarriers due to their small size, aqueous dispersibility, and biocompatibility. The non-covalent attachment of a biocompatible polymer to BN-CNOs is a simple and effective method of creating a scaffold for a novel nanocarrier system as it allows for increased aqueous dispersibility whilst preventing the immune system from recognising the particle as a foreign object. The non-covalent approach also preserves the electronic and structural properties of the BN-CNOs. In this study, we attached a hyaluronic acid-phospholipid (HA-DMPE) conjugate polymer to the BN-CNO’s surface to improve its hydrophilicity and provide targetability toward HA-receptor overexpressing cancer cells. To this end, various ratios of HA-DMPE to BN-CNOs were investigated. The resulting supramolecular systems were characterised via UV-Vis absorption and FTIR spectroscopy, dynamic light scattering, and zeta potential techniques. It was found that the HA-DMPE conjugate polymer was permanently wrapped around the BN-CNO nanoparticle surface. Moreover, the resulting BN-CNO/HA-DMPE supramolecular systems displayed enhanced aqueous solubility compared to unfunctionalised BN-CNOs, with excellent long-term stability observed in aqueous dispersions.

Nanocarriers are rapidly growing in popularity in the field of drug delivery. The ability of nanocarriers to encapsulate and distribute poorly soluble drugs while minimising their undesired effects is significantly advantageous over traditional drug delivery. Nanocarriers can also be decorated with imaging moieties and targeting agents, further incrementing their functionality. Of recent interest as potential nanocarriers are spiropyrans; a family of photochromic molecular switches. Due to their multi-responsiveness to endo- and exogenous stimuli, and their intrinsic biocompatibility, they have been utilised in various drug delivery systems (DDSs) to date. In this review, we provide an overview of the developments in spiropyran-based DDSs. The benefits and drawbacks of utilising spiropyrans in drug delivery are assessed and an outline of spiropyran-based drug delivery systems is presented.

A fluorescent chromophore and a pH-sensitive heterocycle were integrated within a single covalent skeleton to generate four molecular switches with ratiometric fluorescence response. Upon acidification, the pH-sensitive heterocycle opens to shift bathochromically the absorption and emission bands of the fluorescent chromophore. As a result, an equilibrium between two species with resolved fluorescence is established with fast kinetics in aqueous environments. The relative amounts of the two interconverting forms and their relative emission intensities change with pH, providing the opportunity to probe this parameter ratiometrically with fluorescence measurements. Specifically, the resolved emissions of the two species can be collected in separate detection channels of the same microscope to map their ratio across a labeled sample and reconstruct its pH distribution ratiometrically with spatial resolution at the micrometer level. Additionally, the sensitivity of these molecular switches varies with the nature of the heterocyclic ring and with its substituents, allowing the possibility of regulating their response to a given pH range of interest with the aid of chemical synthesis. Thus, a family of valuable fluorescent probes for ratiometric pH sensing in a diversity of samples can emerge from the unique combination of structural and photophysical properties designed into our innovative molecular switches.

Hyaluronic acid (HA) is a ubiquitous biopolymer involved in many pathophysiological roles. One HA receptor, the cluster of differentiation CD44 protein, is often overexpressed in tumor cells. As such, HA has attracted considerable interest in the development of drug delivery formulations, given its intrinsic targetability toward CD44 overexpressing cells. The present study is focused on examining the correlation of HA molecular weight with its targetability properties. A library of conjugates obtained by linking the amino group of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) to the carboxylic residues of HA of different molecular weight (6.4, 17, 51, 200, and 1,500 kDa) were synthesized and fully characterized. The HA-DMPE conjugates were then used to non-covalently functionalize the highly hydrophobic single-walled carbon nanotubes (CNT), and further encapsulate the anticancer drug doxorubicin (DOX). Our results show that the complexes DOX/CNT/HA-DMPE maintain very good and stable dispersibility. Drug release studies indicated a pH-responsive release of the drug from the nanocarrier. Cell viability tests demonstrated that all HA modified CNTs have good biocompatibility, and specific targeting toward cells overexpressing the CD44 receptor. Among all the molecular weights tested, the 200 kDa HA showed the highest increase in cellular uptake and cytotoxic activity. All these promising attributes make CNT/HA200-DMPE a “smart” platform for tumor-targeted delivery of anticancer agents.

Photodynamic therapy is currently one of the most promising approaches for targeted cancer treatment. It is based on responses of vital physiological signals, namely, reactive oxygen species (ROS), which are associated with diseased condition development, such as tumors. This study presents the synthesis, incorporation, and application of a diiodo-BODIPY–based photosensitizer, based on a non-covalent functionalization of carbon nano-onions (CNOs). In vitro assays demonstrate that HeLa cells internalize the diiodo-BODIPY molecules and their CNO nanohybrids. Upon cell internalization and light exposure, the pyrene–diiodo-BODIPY molecules induce an increase of the ROS level of HeLa cells, resulting in remarkable photomediated cytotoxicity and apoptosis. Conversely, when HeLa cells internalize the diiodo-BODIPY/CNO nanohybrids, no significant cytotoxicity or ROS basal level increase can be detected. These results define a first step toward the understanding of carbon nanomaterials that function as molecular shuttles for photodynamic therapeutics, boosting the modulation of the photosensitizer.

Carbon nanomaterials (CNMs) and enzymes differ significantly in terms of their physico-chemical properties—their handling and characterization require very different specialized skills. Therefore, their combination is not trivial. Numerous studies exist at the interface between these two components—especially in the area of sensing—but also involving biofuel cells, biocatalysis, and even biomedical applications including innovative therapeutic approaches and theranostics. Finally, enzymes that are capable of biodegrading CNMs have been identified, and they may play an important role in controlling the environmental fate of these structures after their use. CNMs’ widespread use has created more and more opportunities for their entry into the environment, and thus it becomes increasingly important to understand how to biodegrade them. In this concise review, we will cover the progress made in the last five years on this exciting topic, focusing on the applications, and concluding with future perspectives on research combining carbon nanomaterials and enzymes.

Hyaluronic acid (HA) has been implemented for chemo and photothermal therapy to target tumour cells overexpressing the CD44+ receptor. HA-targeting hybrid systems allows carbon nanomaterial (CNM) carriers to efficiently deliver anticancer drugs, such as doxorubicin and gemcitabine, to the tumour sites. Carbon nanotubes (CNTs), graphene, graphene oxide (GO), and graphene quantum dots (GQDs) are grouped for a detailed review of the novel nanocomposites for cancer therapy. Some CNMs proved to be more successful than others in terms of stability and effectiveness at removing relative tumour volume. While the literature has been focused primarily on the CNTs and GO, other CNMs such as carbon nano-onions (CNOs) proved quite promising for targeted drug delivery using HA. Near-infrared laser photoablation is also reviewed as a primary method of cancer therapy—it can be used alone or in conjunction with chemotherapy to achieve promising chemo-photothermal therapy protocols. This review aims to give a background into HA and why it is a successful cancer-targeting component of current CNM-based drug delivery systems.

Carbon nanomaterials (CNMs) are a fascinating class of materials that have gained considerable interest in recent years. Their favourable biocompatibility, combined with unique chemical and mechanical properties, has attracted scientists from various disciplines. A significant hurdle in their deployment in biomedical applications is their hydrophobicity in their pristine form. This review surveys and discusses existing non-covalent methods of functionalising CNMs with biocompatible dispersants to facilitate their incorporation into aqueous solutions. Different types of dispersants will be examined and compared as well as the factors affecting their efficiency. This work seeks to provide a compilation of the various methods employed in producing biocompatible CNM dispersions.

Boron/nitrogen, co-doped, carbon nano-onions (BN-CNOs) have recently shown great promise as catalysts for the oxygen reduction reaction, due to the improved electronic properties imparted by the dopant atoms; however, the interactions of BN-CNOs with biological systems have not yet been explored. In this study, we examined the toxicological profiles of BN-CNOs and oxidized BN-CNOs (oxi-BN-CNOs) in vitro in both healthy and cancer cell lines, as well as on the embryonic stages of zebrafish (Danio rerio) in vivo. The cell viabilities of both cell lines cells were not affected after treatment with different concentrations of both doped CNO derivatives. On the other hand, the analysis of BN-CNOs and oxidized BN-CNO interactions with zebrafish embryos did not report any kind of perturbations, in agreement with the in vitro results. Our results show that both doped CNO derivatives possess a high biocompatibility and biosafety in cells and more complex systems.

Multishell fullerenes, known as carbon nano-onions (CNOs), have emerged as a platform for bioimaging because of their cell-penetration properties and minimal systemic toxicity. Here, we describe the covalent functionalization of CNOs with a π-extended distyryl-substituted boron dipyrromethene (BODIPY) dye with on/off modulated fluorescence emission activated by an acidic environment. The switching properties are linked to the photoinduced electron transfer (PET) characteristics of the dimethylamino functionalities attached to the BODIPY core. The on/off emission of the fluorescent CNOs is fast and reversible both in solution and in vitro, making this nanomaterial suitable as pH-dependent probes for diagnostic applications.

The developing central nervous system and the blood brain barrier are especially vulnerable and sensitive to different chemicals, including environmental contaminants and drugs. Developmental exposure to these compounds has been involved in several neurological disorders, such as autism spectrum disorders as well as Alzheimer’s and Parkinson’s diseases. Zebrafish (Danio Rerio) have emerged as powerful toxicological model systems that can speed up chemical hazard assessment and can be used to extrapolate neurotoxic effects that chemicals have on humans. Zebrafish embryos and larvae are convenient for high-throughput screening of chemicals, due to their small size, low-cost, easy husbandry, and transparency. Additionally, zebrafish are homologous to other higher order vertebrates in terms of molecular signaling processes, genetic compositions, and tissue/organ structures as well as neurodevelopment. This mini review underlines the potential of the zebrafish as complementary models for developmental neurotoxicity screening of chemicals and describes the different endpoints utilized for such screening with some studies illustrating their use.

Equine bone blocks have osteogenic effects promoting bone regeneration with biocompatibility and osteoconductivity capacity. Human dental pulp stem cells (hDPSCs) can differentiate into osteoblasts enhancing biomineralization with such scaffolds. Melatonin is able to improve bone health and mediate bone formation. Collagenated equine bone blocks were coated with ammonia-functionalized graphene-oxide (G-N) at two different concentrations (2 μg/mL, G-N2; and 10 μg/mL, G-N10). The homogeneity of G-N coating was checked by Raman spectroscopy, whereas thermogravimetric analysis (TGA) allowed us to quantify the amount of G-N deposited on the blocks. The aim of this study was to investigate in vitro the effect of G-N-coated collagenated equine bone blocks on the proliferation and differentiation of hDPSCs with the addition of a melatonin. This evaluation was determined after 7, 14, and 21 days of culture by the expression of specific microRNAs, RUNX2 and SMAD5 gene expression, osteocalcin levels, and histological analysis. The results showed that equine blocks G-N2 and G-N10 and melatonin gave an optimal cell adhesion as shown by histological analysis, and an increase in the hDPSCs osteogenic potential as confirmed by microRNA and gene expression with an increase in osteocalcin levels. This study suggests that equine bone blocks coated with G-N2 and G-N10 and melatonin promote the osteogenic process.

The properties of carbon nano-onions (CNOs) make them attractive electrode materials/additives for the development of low-cost, simple to use and highly sensitive Screen Printed Electrodes (SPEs). Here, we report the development of the first CNO-based ink for the fabrication of low-cost and disposable electrodes, leading to high-performance sensors. Achieving a true dispersion of CNOs is intrinsically challenging and a key aspect of the ink formulation. The screen-printing ink formulation is achieved by carefully selecting and optimising the conductive materials (graphite (GRT) and CNOs), the polymer binder, the organic solvent and the plasticiser. Our CNO/GRT-based screen-printed electrodes consist of an interconnected network of conducting carbon particles with a uniform distribution. Electrochemical studies show a heterogeneous electron transfer rate constant of 1.3 ± 0.7 × 10−3 cm·s−1 and a higher current density than the ferrocene/ferrocenium coupled to a commercial graphite SPEs. In addition, the CNO/GRT SPE can detect dopamine in the concentration range of 10.0–99.9 µM with a limit of detection of 0.92 µM (N = 3). They exhibit a higher analytical sensitivity than the commercial graphite-based SPE, with a 4-fold improvement observed. These results open up the possibility of using high-performing CNO-based SPEs for electrochemical applications including sensors, battery electrodes and electrocatalysis.

Graphene-like (GL) layers, a new graphene-related material (GRM), possess peculiar chemical, colloidal, optical and transport properties. Considering the very recent promising application of GL layers in biomedical and bioelectronic fields, it is of utmost importance to investigate the toxicological profile of these nanomaterials. This study represents an important first report of a complete in vivo toxicity assessment of GL layers on embryonic zebrafish (Danio rerio). Our results show that GL layers do not lead to any perturbations in the different biological parameters evaluated, indicating their good biocompatibility on a vertebrate model. The new insight into the biosafety of GL layers will expand their applications in nanomedicine.

Background: Titanium implant surfaces are continuously modified to improve biocompatibility and to promote osteointegration. Graphene oxide (GO) has been successfully used to ameliorate biomaterial performances, in terms of implant integration with host tissue. The aim of this study is to evaluate the Dental Pulp Stem Cells (DPSCs) viability, cytotoxic response, and osteogenic differentiation capability in the presence of GO-coated titanium surfaces. Methods: Two titanium discs types, machined (control, Crtl) and sandblasted and acid-etched (test, Test) discs, were covalently functionalized with GO. The ability of the GO-functionalized substrates to allow the proliferation and differentiation of DPSCs, as well as their cytotoxic potential, were assessed. Results: The functionalization procedures provide a homogeneous coating with GO of the titanium surface in both control and test substrates, with unchanged surface roughness with respect to the untreated surfaces. All samples show the deposition of extracellular matrix, more pronounced in the test and GO-functionalized test discs. GO-functionalized test samples evidenced a significant viability, with no cytotoxic response and a remarkable early stage proliferation of DPSCs cells, followed by their successful differentiation into osteoblasts. Conclusions: The described protocol of GO-functionalization provides a novel not cytotoxic biomaterial that is able to stimulate cell viability and that better and more quickly induces osteogenic differentiation with respect to simple titanium discs. Our findings pave the way to exploit this GO-functionalization protocol for the production of novel dental implant materials that display improved integration with the host tissue.

Photo-responsive multifunctional nanomaterials are receiving considerable attention for biological applications because of their unique properties. The functionalization of the surface of carbon nanotubes (CNTs) and graphene, among other carbon based nanomaterials, with molecular switches that exhibit reversible transformations between two or more isomers in response to different kind of external stimuli, such as electromagnetic radiation, temperature and pH, has allowed the control of the optical and electrical properties of the nanomaterial. Light-controlled molecular switches, such as azobenzene and spiropyran, have attracted a lot of attention for nanomaterial's functionalization because of the remote modulation of their physicochemical properties using light stimulus. The enhanced properties of the hybrid materials obtained from the coupling of carbon based nanomaterials with light-responsive switches has enabled the fabrication of smart devices for various biological applications, including drug delivery, bioimaging and nanobiosensors. In this review, we highlight the properties of photo-responsive carbon nanomaterials obtained by the conjugation of CNTs and graphene with azobenzenes and spiropyrans molecules to investigate biological systems, devising possible future directions in the field.

The toxicological effects of pristine and chemically modified carbon nano-onions (CNOs) on the development of the freshwater polyp Hydra vulgaris were investigated in order to elucidate the ecotoxicological effects of CNOs. Chemical modifications of the CNOs were accomplished by surface functionalization with benzoic acid, pyridine and pyridinium moieties. thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR) and Raman spectroscopy confirmed the covalent surface functionalization of CNOs. Hydra specimens were exposed to the carbon nanomaterials by prolonged incubation within their medium. Uptake was monitored by optical microscopy, and the toxicological effects of the CNOs on Hydra behavior, morphology, as well as the long-term effects on the development and reproductive capability were examined. The obtained data revealed the absence of adverse effects of CNOs (in the range 0.05–0.1 mg/L) in vivo at the whole animal level. Together with previously performed in vitro toxicological analyses, our findings indicate the biosafety of CNOs and the feasibility of employing them as materials for biomedical applications.

This review focuses on the development of multi-layer fullerenes, known as carbon nano-onions (CNOs). First, it briefly summarizes the most important synthetic pathways for their preparation and their properties and it gives the reader an update over new developments in the recent years. This is followed by a discussion of the published synthetic procedures for CNO functionalization, which are of major importance when elucidating future applications and addressing drawbacks for possible applications, such as poor solubility in common solvents. Finally, it gives an overview over the fields of application, in which CNO materials were successfully implemented.

Carbon nano-onions (CNOs) possess favorable properties that make them suitable for biomedical applications, including their small size, ready surface modification, and good biocompatibility. Here, we report the covalent immobilization of a synthetic glycopeptide and the protein bovine serum albumin (BSA) onto the surface of carbon nano-onions using the maleimide−thiol “addition reaction”. The glycopeptide and BSA are readily transported inside different cell lines, together with carbon nano-onions, through the endocytosis pathway. Our results show that carbon nano-onions are excellent scaffolds for glycopeptides and proteins immobilization and act as intracellular carriers for these biomolecules. These findings open new perspectives in the application of carbon nano-onions as intracellular transporters in diverse biomedical applications.

Carbon nanomaterials (CNMs) are increasingly employed in nanomedicine as carriers for intracellular transport of drugs, imaging probes, and therapeutics agents, thanks to their unique optical and physicochemical properties. However, a better understanding about the effects of CNMs on a vertebrate model at the whole animal level is required. In this study, we compare the toxicity of oxidized carbon nano-onions (oxi-CNOs), oxidized carbon nano-horns (oxi-CNHs) and graphene oxide (GO) in zebrafish (Danio rerio). We evaluate the possible effects of these nanomaterials on zebrafish development by assessing different end-points and exposure periods.