[Show abstract][Hide abstract] ABSTRACT: A single organism comprises diverse types of cells. To acquire a detailed understanding of the biological functions of each cell, comprehensive control and analysis of homeostatic processes at the single-cell level are required. In this study, we develop a new type of light-driven nanomodulator comprising dye-functionalized carbon nanohorns (CNHs) that generate heat and reactive oxygen species under biologically transparent near-infrared (NIR) laser irradiation. By exploiting the physicochemical properties of the nanohorns, cellular calcium ion flux and membrane currents were successfully controlled at the single-cell level. In addition, the nanomodulator allows a remote bioexcitation of tissues during NIR laser exposure making this system a powerful tool for single-cell analyses and innovative cell therapies.
Angewandte Chemie International Edition 10/2014; · 11.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nanocomposites combining multiple functionalities in one single nanoobject hold a lot of promises for biomedical applications. In this work carbon nanotubes (CNTs) were filled with ferrite nanoparticles (NPs) to develop the magnetic manipulation of the nanotubes and their theranostic applications. The challenges were both the filling of CNTs with a high amount of magnetic NPs and their functionalization to form biocompatible water suspensions. We are here proposing a filling process using CNTs as nanoreactors for high yield in situ growth of ferrite NPs into the inner carbon cavity. At first, NPs were formed inside the nanotubes by thermal decomposition of an iron stearate precursor. A second filling step was then performed with iron or cobalt stearate precursors to enhance the encapsulation yield and block the formed NPs inside the tubes. Water suspensions were then obtained by addition of amino groups via the covalent functionalization of the external surface of the nanotubes. Microstructural and magnetic characterizations confirmed the confinement of NPs into the anisotropic structure of CNTs making them suitable for magnetic manipulations and MRI detection. Interactions of highly water dispersible CNTs with tumor cells could be modulated by magnetic fields without toxicity, allowing to control their orientation within the cell and to induce submicron magnetic stirring. The magnetic properties were also used to quantify CNTs cellular uptake by measuring the cell magnetophoretic mobility. Finally, the photothermal ablation of tumor cells could be enhanced by magnetic stimulus, harnessing the hybrid properties of NP loaded-CNTs.
[Show abstract][Hide abstract] ABSTRACT: Among targeted delivery systems, platforms with nanosize dimensions, such as carbon nanomaterials (CNMs) and metal nanoparticles (NPs), have shown great potential in biomedical applications. They have received considerable interest in recent years, especially with respect to their potential utilization in the field of cancer diagnosis and therapy. The multifunctionalization of nanomaterials provides opportunities to use them as multimodal agents for theranostics, a combination of therapy and diagnosis. Carbon nanotubes and graphene are within the most widely used CNMs because of their unique structural and physico-chemical properties. Their high specific surface area allows an efficient drug loading and the possibility of functionalization with various bioactive molecules. In addition, CNMs are ideal platforms for the attachment of NPs. In the biomedical field, NPs have also shown tremendous promises in drug delivery, non-invasive tumor imaging and early detection due to their optical and magnetic properties. NP/CNM hybrids not only combine the unique properties of the NPs and CNMs, but they also exhibit new properties arising from the interactions between the two entities. In this review, the preparation of CNMs conjugated to different types of metal NPs and their applications in diagnosis, imaging, therapy, and theranostics are presented.
British Journal of Pharmacology 10/2014; · 5.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multifunctional carbon nanohorn (CNH) complexes were synthesized using oxidized CNH, magnetite (MAG) nanoparticles, and polyethyleneimine (PEI). The ferromagnetic MAG nanoparticles were loaded onto CNH (MAG-CNH) using iron(II) acetate and subsequent heat treatment. Chemical functionalization of the MAG-CNH complexes with PEI improved their water-dispersibility and allowed further conjugation with a fluorophore. The application of an external magnetic field significantly intensified the targeted vectorization of CNH complexes into human cervical cancer (HeLa) cells. Following cell uptake, laser irradiation of the cells showed a significant enhancement in the photothermal effects of CNHs leading to cell death. We have confirmed that the photothermal properties and ferromagnetic characteristics of CNH complexes show efficient cell elimination. The present study is an essential step toward the development of an innovative cancer therapy and a highly sensitive detection of cancer cells at the single-cell level.
Chemistry - An Asian Journal 10/2014; · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present the science and technology roadmap (STR) for graphene, related two-dimensional (2d) crystals, and hybrid systems, targeting an evolution in technology, with impacts and benefits reaching into most areas of society. The roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. In this document we provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlithing the roadmap to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries: from flexible, wearable and transparent electronics to high performance computing and spintronics.
[Show abstract][Hide abstract] ABSTRACT: Given the promise of carbon nanotubes (CNTs) for photothermal therapy, drug delivery, tissue engineering, and gene therapy, there is a need for non-invasive imaging methods to monitor CNT distribution and fate in the body. In this study, non-ionizing whole-body high field magnetic resonance imaging (MRI) is used to follow the distribution of water-dispersible non-toxic functionalized CNTs administrated intravenously to mice. Oxidized CNTs are endowed with positive MRI contrast properties by covalent functionalization with the chelating ligand diethylenetriaminepentaacetic dianhydride (DTPA), followed by chelation to Gd3+. The structural and magnetic properties, MR relaxivities, cellular uptake, and application for MRI cell imaging of Gd-CNTs in comparison to the precursor oxidized CNTs are evaluated. Despite the intrinsic T2 contrast of oxidized CNTs internalized in macrophages, the anchoring of paramagnetic gadolinium onto the nanotube sidewall allows efficient T1 contrast and MR signal enhancement, which is preserved after CNT internalization by cells. Hence, due to their high dispersibility, Gd-CNTs have the potential to produce positive contrast in vivo following injection into the bloodstream. The uptake of Gd-CNTs in the liver and spleen is assessed using MRI, while rapid renal clearance of extracellular Gd-CNTs is observed, confirming the evidences of other studies using different imaging modalities.
[Show abstract][Hide abstract] ABSTRACT: Carbon nanotubes (CNTs) exhibit unique properties which have led to their applications in the biomedical field as novel delivery systems for diagnosis and therapy purposes. We have previously reported that the degree of functionalization of CNTs is a key factor determining their biological behaviour. The present study broadens the spectrum by investigating the impact of the diameter of CNTs using two series of multi-walled CNTs (MWNTs) with distinct differences in their diameters. Both MWNTs were doubly functionalized by 1,3-dipolar cycloaddition and amidation reactions, allowing the appended functional groups to be further conjugated with radionuclide chelating moieties and antibodies or antibody fragments. All constructs possessed comparable degree of functionalization and were characterized by thermogravimetric analysis, transmission electron microscopy, gel electrophoresis and surface plasmon resonance. The MWNT conjugates were radio-labelled with indium-111, which thereby enabled in vivo single photon emission computed tomography/computed tomography (SPECT/CT) imaging and organ biodistribution study using γ-scintigraphy. The narrow MWNTs (average diameter: 9.2 nm) demonstrated enhanced tissue affinity including non-reticular endothelial tissues compared to the wider MWNTs (average diameter: 39.5 nm). The results indicate that the higher aspect ratio of narrow MWNTs may be beneficial for their future biological applications due to higher tissue accumulation.
[Show abstract][Hide abstract] ABSTRACT: Carbon nanotubes (CNTs) are recognized as promising nanomaterials for technological advancement. However, the stigma of structural similarity with asbestos fibers has slowed down progress of CNTs in nanomedicine. Nevertheless, it also prompted thorough studies that have revealed that functionalized CNTs (fCNTs) can biologically behave in a very different and safer manner. Here we review pristine and fCNT fate in biological settings, focusing on the importance of protein interaction, formation of the protein corona, and modulation of immune response. The emerging consensus on the desirable fCNT properties to achieve immunological neutrality, and even biodegradation, shows great promise for CNT adoption in medicine.
[Show abstract][Hide abstract] ABSTRACT: Dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. Maleimido groups at the periphery of the scaffold were used to covalently attach the peptide called P140, a therapeutic phosphopeptide controlling disease activity in systemic lupus, both in mice and patients. Biotinylation of the trimers at the focal point was performed using click chemistry and the conjugates were studied in terms of solubility, binding affinity to its receptor, the HSPA8/HSC70 chaperone protein, effect on HSPA8 folding property and in vivo activity. The results showed that the trimerization of P140 peptide does not trigger aggregation or steric hindrances during the interaction with HSPA8 protein. Compared to the monomeric cognate peptide, the trivalent P140 peptide displayed the same capacity, in vitro, to down-regulate HSPA8 activity and, in vivo in MRL/lpr lupus-prone mice, to reduce abnormal blood hypercellularity. The control trimer synthesized with the same scaffold and a scrambled sequence of P140 showed no effect in vivo. This work reveals that adamantane-based scaffolds with a well-defined spatial conformation are promising trivalent systems for molecular recognition and for biomedical applications.
[Show abstract][Hide abstract] ABSTRACT: Spaceflights lead to dysregulation of the immune cell functionality affecting the expression of activation markers and cytokine production. Short oxidized multi-walled carbon nanotubes functionalized by 1,3-dipolar cycloaddition have been reported to activate immune cells. In this Communication we have performed surface marker assays and multiplex ELISA on primary monocytes and T cells under microgravity. We have discovered that carbon nanotubes, through their immunostimulatory properties, are able to fight spaceflight immune system dysregulations.
[Show abstract][Hide abstract] ABSTRACT: Carbon-based nanomaterials, including carbon nanotubes and graphene, have created great attention in the scientific community for their unique physico-chemical properties, which could be also promising in many biomedical-related fields. In particular, their low cytotoxicity, achieved when properly functionalized, along with the possibility to link multiple bioactive molecules, realistically allows envisaging their potential use as therapeutic platform. In this context, the immune system and immune responses play an important role in our organism, as they are involved either directly or indirectly in many diseases. Therefore, the possibility to prevent or block a disease by controlling and/or modulating the immune responses has become one important task in nanomedicine. In this feature article the advantages to use carbon-based materials in immunotherapy are presented. Important goals obtained using carbon nanotubes and graphene are described, highlighting the promising use of these nanomaterials in cancer treatment, imaging and vaccine development. The capacity of functionalized carbon nanotubes to modulate the immune responses is also discussed, highlighting the current state of the art and the future developments on this subject.
[Show abstract][Hide abstract] ABSTRACT: We explore at a world level the awareness of nanotechnology expressed through the most popular online social media: Facebook. We aimed at identifying future trends, the most interested countries and the public perception of ethics, funding and economic issues. We found that graphene and carbon nanotubes are the most followed nanomaterials. Our poll showed that the continents with the most interest are Asia and Africa. A total of 43% would like to have a world commission regulating nanomedicine. In addition, 43% would give priority to theranostics. Over 90% believe that nanomedicine has an economic impact. Finally, we observed that the continents of living and origin of poll contributors correlated with ethic and funding opinions. This study highlights the potential of online social media to influence scientific communities, grant committees and nanotechnology companies, spreading nanotechnology awareness in emerging countries and among new generations.
[Show abstract][Hide abstract] ABSTRACT: Graphing graphene: Because the naming of graphene-based materials (GBMs) has led to confusion and inconsistency, a classification approach is necessary. Three physical-chemical properties of GBMs have been defined by the GRAPHENE Flagship Project of the European Union for the unequivocal classification of these materials (see grid).
Angewandte Chemie International Edition in English 06/2014; 53(30). · 13.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been recently proposed that nanomaterials, alone or in concert with their specific biomolecular conjugates, can be used to directly modulate the immune system, therefore offering a new tool for the enhancement of immune-based therapies against infectious disease and cancer. Here, we revised the publications on the impact of functionalized carbon nanotubes (f-CNTs), graphene and carbon nanohorns on immune cells. Whereas f-CNTs are the nanomaterial most widely investigated, we noticed a progressive increase of studies focusing on graphene in the last couple of years. The majority of the works (56%) have been carried out on macrophages, following by lymphocytes (30% of the studies). In the case of lymphocytes, T cells were the most investigated (22%) followed by monocytes and dendritic cells (7%), mixed cell populations (peripheral blood mononuclear cells, 6%), and B and natural killer (NK) cells (1%). Most of the studies focused on toxicity and biocompatibility, while mechanistic insights on the effect of carbon nanotubes on immune cells are generally lacking. Only very recently high-throughput gene-expression analyses have shed new lights on unrecognized effects of carbon nanomaterials on the immune system. These investigations have demonstrated that some f-CNTs can directly elicitate specific inflammatory pathways. The interaction of graphene with the immune system is still at a very early stage of investigation. This comprehensive state of the art on biocompatible f-CNTs and graphene on immune cells provides a useful compass to guide future researches on immunological applications of carbon nanomaterials in medicine.
Journal of Translational Medicine 05/2014; 12(1):138. · 3.99 Impact Factor