Radiolabeling, whole-body single photon emission computed tomography/computed tomography imaging, and pharmacokinetics of carbon nanohorns in mice.

In this work, we report that the biodistribution and excretion of carbon nanohorns (CNHs) in mice are dependent on their size and functionalization. Small-sized CNHs (30-50 nm; S-CNHs) and large-sized CNHs (80-100 nm; L-CNHs) were chemically functionalized and radiolabeled with [(111)In]-diethylenetriaminepentaacetic acid and intravenously injected into mice. Their tissue distribution profiles at different time points were determined by single photon emission computed tomography/computed tomography. The results showed that the S-CNHs circulated longer in blood, while the L-CNHs accumulated faster in major organs like the liver and spleen. Small amounts of S-CNHs- and L-CNHs were excreted in urine within the first few hours postinjection, followed by excretion of smaller quantities within the next 48 hours in both urine and feces. The kinetics of excretion for S-CNHs were more rapid than for L-CNHs. Both S-CNH and L-CNH material accumulated mainly in the liver and spleen; however, S-CNH accumulation in the spleen was more prominent than in the liver.journal article20162016 07 22importe

Diameter-dependent release of a cisplatin pro-drug from small and large functionalized carbon nanotubes

The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes’ inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(IV) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(IV)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(IV)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(IV)@CNT exposure demonstrate that they can promote drug accumulation inside cells in comparison with treatment with the free complex. To conclude, our study shows that CNTs are promising nanocarriers to improve the accumulation of a chemotherapeutic drug and its slow release inside tumor cells, by tuning the CNT diameter, without inducing a high inflammatory response

Intracellular degradation of functionalized carbon nanotube/iron oxide hybrids is modulated by iron via Nrf2 pathway.

The in vivo fate and biodegradability of carbon nanotubes is still a matter of debate despite tremendous applications. In this paper we describe a molecular pathway by which macrophages degrade functionalized multi-walled carbon nanotubes (CNTs) designed for biomedical applications and containing, or not, iron oxide nanoparticles in their inner cavity. Electron microscopy and Raman spectroscopy show that intracellularly-induced structural damages appear more rapidly for iron-free CNTs in comparison to iron-loaded ones, suggesting a role of iron in the degradation mechanism. By comparing the molecular responses of macrophages derived from THP1 monocytes to both types of CNTs, we highlight a molecular mechanism regulated by Nrf2/Bach1 signaling pathways to induce CNT degradation via NOXjournal article2017 Jan 252017 01 25importe

Kinetics of functionalised carbon nanotube distribution in mouse brain after systemic injection: Spatial to ultra-structural analyses.

Earlier studies proved the success of using chemically functionalised multi-walled carbon nanotubes (f-MWNTs) as nanocarriers to the brain. Little insight into the kinetics of brain distribution of f-MWNTs in vivo has been reported. This study employed a wide range of qualitative and quantitative techniques with the aim of shedding the light on f-MWNT's brain distribution following intravenous injection. γ-Scintigraphy quantified the uptake of studied radiolabelled f-MWNT in the whole brain parenchyma and capillaries while 3D-single photon emission computed tomography/computed tomography imaging and autoradiography illustrated spatial distribution within various brain regions. Raman and multiphoton luminescence together with transmission electron microscopy confirmed the presence of intact f-MWNT in mouse brain, in a label-free manner. The results evidenced the presence of f-MWNT in mice brain parenchyma, in addition to brain endothelium. Such information on the rate and extent of regional and cellular brain distribution is needed before further implementation into neurological therapeutics can be made.journal articleresearch support, non-u.s. gov't2016 Feb 282015 12 30importe

Designing multimodal carbon nanotubes by covalent multi-functionalization.

Carbon nanotubes (CNTs) are a unique tool in nanotechnology owing to their exceptional properties that offer a variety of opportunities for applications in different fields. Nevertheless, their low dispersibility in organic solvents and in aqueous media hampers their development. The functionalization of their surface allows overcoming this issue, while exploiting and tuning their properties. Thanks to their high specific surface area, multi-functionalization strategies give the possibility to conjugate several copies of different molecules to endow the nanotubes with multiple functionalities. In this context, this review wishes to focus on the preparation of multimodal CNTs designed by covalent multi-functionalization. More specifically, we describe the different approaches that have been developed to prepare multi-functionalized CNTs through double and triple covalent functionalization of the nanotube framework. We also emphasize the strategies used to control the derivatization of multi-functionalized CNTs with molecules of interest mainly via sequential or simultaneous methodologies.journal article2016 Nov 10importe

Carbon nanomaterials as new tools for immunotherapeutic applications

Carbon-based nanomaterials, including carbon nanotubes and graphene, have gained great attention in the scientific community due to 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 a 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 an important task in nanomedicine. In this feature article the advantages of using carbon-based materials in immunotherapy are presented. Important goals achieved 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

Graphene-based nanomaterials for nanobiotechnology and biomedical applications.

Graphene family nanomaterials are currently being extensively explored for applications in the field of nanotechnology. The unique intrinsic properties treasured in their simple molecular design and their ability to work in coherence with other existing nanomaterials make graphene family nanomaterials the most promising candidates for different types of applications. This review highlights the scope and utility of these multifaceted nanomaterials in nanobiotechnology and biomedicine. In a tandem approach, this review presents the smooth inclusion of these nanomaterials into existing designs for creating efficient working models at the nanoscale level as well as discussing their broad future possibilities.journal articleresearch support, non-u.s. gov'treview2013 Octimporte

A Flexible Method for Covalent Double Functionalization of Graphene Oxide

A method for the double functionalization of graphene oxide (GO) under mild alkaline conditions has been developed. Two functional groups were covalently linked to GO in two steps: the first group was attached by an epoxide ring-opening reaction and the second, bearing an amine function, was covalently conjugated to benzoquinone attached to the GO. The doubly functionalized GO was characterized by several techniques, confirming the sequential covalent modification of the GO surface with two different functional groups. This method is straightforward and the reaction conditions are mild, allowing preservation of the structure and properties of GO. This strategy could be exploited to prepare multifunctional GO conjugates with potential applications in many fields ranging from materials science to biomedicine

Carbon nanomaterials combined with metal nanoparticles for theranostic applications.

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 many functions of nanomaterials provide opportunities to use them as multimodal agents for theranostics, a combination of therapy and diagnosis. Carbon nanotubes and graphene are some of the most widely used CNMs because of their unique structural and physicochemical properties. Their high specific surface area allows for 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 potential for use in drug delivery, non-invasive tumour 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 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.journal articleresearch support, non-u.s. gov'treview2015 Feb2015 01 12importe

Graphene and the immune system: Challenges and potentiality.

In the growing area of nanomedicine, graphene-based materials (GBMs) are some of the most recent explored nanomaterials. For the majority of GBM applications in nanomedicine, the immune system plays a fundamental role. It is necessary to well understand the complexity of the interactions between GBMs, the immune cells, and the immune components and how they could be of advantage for novel effective diagnostic and therapeutic approaches. In this review, we aimed at painting the current picture of GBMs in the background of the immune system. The picture we have drawn looks like a cubist image, a sort of Picasso-like portrait looking at the topic from all perspectives: the challenges (due to the potential toxicity) and the potentiality like the conjugation of GBMs to biomolecules to develop advanced nanomedicine tools. In this context, we have described and discussed i) the impact of graphene on immune cells, ii) graphene as immunobiosensor, and iii) antibodies conjugated to graphene for tumor targeting. Thanks to the huge advances on graphene research, it seems realistic to hypothesize in the near future that some graphene immunoconjugates, endowed of defined immune properties, can go through preclinical test and be successfully used in nanomedicine.journal articlereview2016 Oct 012016 05 25importe