The Glitter of Carbon Nanostructures in Hybrid/Composite Hydrogels for Medicinal Use

In recent years, we have witnessed to fast developments in the medicinal field of hydrogels containing various forms of integrated nanostructured carbon that adds interesting mechanical, thermal, and electronic properties. Besides key advances in tissue engineering (especially for conductive tissue, such as for the brain and the heart), there has been innovation also in the area of drug delivery on-demand, with engineered hydrogels capable of repeated response to light, thermal, or electric stimuli. This mini-review focusses on the most promising developments as applied to the gelation of protein/ peptide (including self-assembling amino acids and low-molecular-weight gelators), polysaccharide, and/or synthetic polymer components in medicine. The emerging field of graphene-only hydrogels is also briefly discussed, to give the reader a full flavor of the rising new paradigms in medicine that are made possible through the integration of nanostructured carbon (e.g., carbon nanotubes, nanohorns, nanodiamonds, fullerene, etc.). Nanocarbons are offering great opportunities to bring on a revolution in therapy that the modern medicinal chemist needs to master, to realise their full potential into powerful therapeutic solutions for the patient

Biological Applications of Fullerene Derivatives: A Brief Overview

Starting soon after the production of fullerenes in 1990, many efforts have been devoted to the application of C60 and its derivatives. In fact, [60]fullerene possesses a variety of interesting biological properties, such as HIV-P inhibition, DNA photocleavage, neuroprotection, apoptosis, etc. Unfortunately, the low solubility in biological fluids limits the use of these compounds as new pharmacophores for structure-activity relationship studies in medicinal Chemistry. This article briefly summarizes recent studies on the functionalization of C60 aimed at increasing water solubility as well as the preliminary studies performed on biological targets. In particular, the HIV-P inhibition, DNA photocleavage and antibacterial activity are discussed

Investigation into the stability of WEE1 kinase in plants

Phosphoregulation is essential for the control of cell division. In yeasts and animals, premature entry into mitosis is prevented by the inhibitory phosphorylation of CDK by WEE1 kinase. WEE1 homologues have been identified in several species of higher plant, including Arabidopsis and tobacco. However, while WEE1 function has been confirmed in the DNA replication checkpoint in higher plants, a role for the protein in the G2/M transition during an unperturbed plant cell cycle is yet to be identified. To address this issue, the further characterisation of Arabidopsis WEE1 was completed, particularly focussing on the localisation and stability of the protein. A GFP-Arath;WEE1 construct under the 35S promoter was transformed into both Arabidopsis plants and the tobacco BY-2 cell line, and a nuclear localisation of the protein at interphase was confirmed. Additionally, the study of WEE1 subcellular localisation in different cell cycle phases revealed that the protein was absent during metaphase. Interestingly, levels of WEE1 degradation varied in different Arabidopsis root tissues, and the protein was absent in lateral root primordia. The proteasome inhibitor MG132 was used to demonstrate that Arath;WEE1 is degraded via the 26S proteasome pathway, as in yeasts and animals. Bimolecular fluorescence complementation confirmed an interaction between Arath;WEE1 and the F-box protein Arath;SKIP1 in vivo, which may target Arath;WEE1 for degradation. Tobacco BY-2 cells were stably co-transformed with BiFC constructs to facilitate the study of any changes in this interaction during the cell cycle. There was again no evidence of the interaction during metaphase, but a return of the signal during anaphase and telophase. The root phenotype of an Arath;SKIP1 knockdown line suggested that this F-box protein may target Arath;WEE1 for degradation early in development, but this requires confirmation. The work presented in this thesis describes, to my knowledge, the first investigation into the stability of Arath;WEE1 protein.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A Cationic [60] Fullerene Derivative Reduces Invasion and Migration of HT-29 CRC Cells in Vitro at Dose Free of Significant Effects on Cell Survival

Nanomaterials with unique characteristics exhibit favorable therapeutic and diagnostic properties, implying their enormous potential as biomedical candidates. C60 has been used in gene- and drug-delivery, as imaging agents, and as photosensitizers in cancer therapy. In this study, the influences of a cationic functionalized fullerene on cellular behavior of human colorectal cancer cell line (HT-29) were investigated. Results indicated that HT-29 treated with the studied compound showed a lower sensitivity but a significant impairment in migration and invasion by interfering with the activities of matrix metalloproteinases (MMP-2 and 9). The presence of fullerene also altered the capacity of adhesion-related proteins to perform their activity, thereby inducing dramatically adverse effects on the cell physiological functions such as cell adhesion. Thus, our study suggests that this compound is a new potential anti-metastatic effector and a therapeutic component for malignant colorectal cancer

Filling Single-Walled Carbon Nanotubes with Lutetium Chloride : A Sustainable Production of Nanocapsules Free of Nonencapsulated Material

Filled carbon nanotubes are of interest for a wide variety of applications ranging from sensors to magnetoelectronic devices and going through the development of smart contrast and therapeutic agents in the biomedical field. In general, regardless of the method employed, bulk filling of carbon nanotubes results in the presence of a large amount of external nonencapsulated material. Therefore, further processing is needed to achieve a sample in which the selected payload is present only in the inner cavities of the nanotubes. Here, we report on a straightforward approach that allows the removal of nonencapsulated compounds in a time efficient and environmentally friendly manner, using water as a "green" solvent, while minimizing the residual waste. The results presented herein pave the way toward the production of large amounts of high-quality closed-ended filled nanotubes, also referred to as carbon nanocapsules, readily utilizable in the foreseen applications

Nanocellulose/Fullerene Hybrid Films Assembled at the Air/Water Interface as Promising Functional Materials for Photo-Electrocatalysis

Cellulose nanomaterials have been widely investigated in the last decade, unveiling attractive properties for emerging applications. The ability of sulfated cellulose nanocrystals (CNCs) to guide the supramolecular organization of amphiphilic fullerene derivatives at the air/water interface has been recently highlighted. Here, we further investigated the assembly of Langmuir hybrid films that are based on the electrostatic interaction between cationic fulleropyrrolidines deposited at the air/water interface and anionic CNCs dispersed in the subphase, assessing the influence of additional negatively charged species that are dissolved in the water phase. By means of isotherm acquisition and spectroscopic measurements, we demonstrated that a tetra-sulfonated porphyrin, which was introduced in the subphase as anionic competitor, strongly inhibited the binding of CNCs to the floating fullerene layer. Nevertheless, despite the strong inhibition by anionic molecules, the mutual interaction between fulleropyrrolidines at the interface and the CNCs led to the assembly of robust hybrid films, which could be efficiently transferred onto solid substrates. Interestingly, ITO-electrodes that were modified with five-layer hybrid films exhibited enhanced electrical capacitance and produced anodic photocurrents at 0.4 V vs Ag/AgCl, whose intensity (230 nA/cm2) proved to be four times higher than the one that was observed with the sole fullerene derivative (60 nA/cm2)

Evaluation of the efficacy of carbon nanotubes for delivering peptides into mitochondria

Mitochondrial (mt) diseases are devastating neurodegenerative pathologies due tomutations in nuclear or mt genes. Among mtDNA pathogenic mutations, more than one half have been identified in transfer RNA (tRNA) genes. These are responsible for a wide range of pathologies including myopathies, encephalopathies, cardiomyopathies and deafness for which no effective treatment is available at present. Therefore, new strategies to suppress their damaging effects are required to envisage therapeutic approaches for these diseases. Here we report data for carbon nanotube (CNT) derivatives showing that the conjugates bearing a specific peptide sequence are able to target the mitochondria in yeast and human monocyte cells while the control derivative without the peptide diffuses into the cytoplasm. Moreover the compounds do not affect cellular viability and cytotoxicity both in vitro and in vivo. Toxicity of the constructs is also assessed on the simple pluricellular model Caenorhabditis elegans

A tool box to ascertain the nature of doping and photoresponse in single-walled carbon nanotubes

The effect of doping on the electronic properties in bulk single-walled carbon nanotube (SWCNT) samples is studied for the first time using a new in situ Raman spectroelectrochemical method, and further verified by DFT calculations and photoresponse. We use p-/n-doped SWCNTs prepared by diazonium reactions as a versatile chemical strategy to control the SWCNT behavior. The measured and calculated data testify an acceptor effect of 4-aminobenzenesulfonic acid (p-doping), and a donor effect (n-doping) in the case of benzyl alcohol. In addition, pristine and covalently functionalized SWCNTs were used for the preparation of photoactive film electrodes. The photocathodic current in the photoelectrochemical cell is consistently modulated by the doping group. These results validate the in situ Raman spectroelectrochemistry as a unique tool box for predicting the electronic properties of functionalized SWCNTs in the form of thin films and their operational functionality in thin film devices for future optoelectronic applications

Iron-related toxicity of single-walled carbon nanotubes and crocidolite fibres in human mesothelial cells investigated by Synchrotron XRF microscopy

Carbon nanotubes (CNTs) are promising products in industry and medicine, but there are several human health concerns since their fibrous structure resembles asbestos. The presence of transition metals, mainly iron, in the fibres seems also implicated in the pathogenetic mechanisms. To unravel the role of iron at mesothelial level, we compared the chemical changes induced in MeT-5A cells by the exposure to asbestos (crocidolite) or CNTs at different content of iron impurities (raw-SWCNTs, purified- and highly purified-SWCNTs). We applied synchrotron-based X-Ray Fluorescence (XRF) microscopy and soft X-ray imaging (absorption and phase contrast images) to monitor chemical and morphological changes of the exposed cells. In parallel, we performed a ferritin assay. X-ray microscopy imaging and XRF well localize the crocidolite fibres interacting with cells, as well as the damage-related morphological changes. Differently, CNTs presence could be only partially evinced by low energy XRF through carbon distribution and sometimes iron co-localisation. Compared to controls, the cells treated with raw-SWCNTs and crocidolite fibres showed a severe alteration of iron distribution and content, with concomitant stimulation of ferritin production. Interestingly, highly purified nanotubes did not altered iron metabolism. The data provide new insights for possible CNTs effects at mesothelial/pleural level in humans

Lithium halide filled carbon nanocapsules: Paving the way towards lithium neutron capture therapy (LiNCT)

Neutron capture therapy (NCT) is a form of radiotherapy that exploits the potential of some specific isotopes to capture thermal neutrons and subsequently yield high linear energy transfer (LET) particles, suitable for cancer treatment. Recently, relevant technological improvements have been made in terms of accelerators as suitable neutron sources for NCT at hospitals. However, low selective delivery of current drugs to cancer cells remains as the main challenge for successful clinical application of NCT. This work presents an innovative and previously unexplored approach for the design of nanotherapeutic NCT agents. Herein, a new concept based on carbon nanomaterials that seal 6Li active NCT nuclides is investigated. The 6Li active species are located in the inner cavity of the nanocarrier (carbon nanohorns or carbon nanotubes) and therefore, completely protected from the biological environment, avoiding toxicity and degradation. After encapsulation of the active cargo, the external surface of the nanocarrier is modified for improved biocompatibility. The developed 6Li-filled carbon nanohorns offered the possibility to explore 6Li compounds as active NCT agents by delivering therapeutic doses to cancer cells. We envisage that nanoencapsulation of 6Li can trigger the successful development and implementation of Lithium Neutron Cancer Therapy (LiNCT).G. T. acknowledges funding from ERC Consolidator Grant NEST (725743). G.G. gratefully acknowledges the funding by the Portuguese Science Foundation (FCT) for Programme Stimulus of Scientific Employment – Individual Support (CEECIND/01913/2017), financial support of project CARBONCT (2022.03596.PTDC), TEMA UIDB/00481/2020 and UIDP/00481/2020; and CENTRO-01-0145-FEDER-022083 - Centro Portugal Regional Operational Programme (Centro2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund. In addition, support through the project IF/00894/2015 and within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 & LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC) is gratefully acknowledged. We acknowledge funding by INFN (CSN5)-project ENTER_BNCT. ICMAB and ICN2 acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (Spain), through the “Severo Ochoa” Programme for Centres of Excellence in R&D (CEX2019-000917-S and CEX2021-001214-S respectively). ICN2 is supported by CERCA programme. We acknowledge funding from Generalitat de Catalunya (2021-SGR-00439, 2017 SGR 327). M.Ll. has carried out this work in the framework of the Doctoral Degree Program in Materials Science of the Universitat Autònoma de Barcelona. We acknowledge fruitful discussions with Manuel Altabas and support with the XPS analysis by Guillaume Sauthier.With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).Peer reviewe