Biomedical applications of functionalised carbon nanotubes

The organic functionalisation of carbon nanotubes can improve substantially their solubility and biocompatibility profile; as a consequence, their manipulation and integration into biological systems has become possible so that functionalised carbon nanotubes hold currently strong promise as novel systems for the delivery of drugs, antigens and genes.     

碳纳米管在药物和基因转运领域的研究进展

当前,国内外的许多研究小组都致力于开发出新型有效的药物和基因转运系统,用于改善多种治疗因子的药理学作用并降低其毒性。在纳米材料这一类中,碳纳米管（Carbon Nanotubes, CNTs）正逐步引起人们的关注。功能化的CNTs的两个关键优势在于它具有很强的细胞穿透能力和较低的细胞毒性,使其在药物和基因转运领域中的应用成为可能。CNTs可通过形成稳定的共价键或形成以非共价键为基础的超分子结合物来运载肽类、蛋白质、核酸和药物等活性分子,并将其运送至特定的组织、器官中以表达特殊的生物学功能。针对这一研究热点,本文综述了近几年国内外关于碳纳米管在药物和基因转运领域中的应用进展,并探讨了其毒性,以期为这一领域中的研究工作者提供参考。     

Hyaluronic Acid-Conjugated Carbon Nanomaterials for Enhanced Tumour Targeting Ability

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.     

Targeting carbon nanotubes against cancer

The use of carbon nanotubes (CNTs) as polyvalent tools for cancer treatment is progressing at a very fast pace. The most promising approach is the targeted delivery of drugs, designed to selectively direct the therapeutic treatment towards the tumours. CNTs may offer several advantages to overcome one of the main limitations of most existing anticancer therapies, namely the lack of selectivity. Herein, an account of the existing literature on CNT-based nanomedicine for cancer treatment is given. The most significant results obtained so far in the field of drug delivery are presented for many anticancer chemotherapeutics (doxorubicin, methotrexate, taxanes, platinum analogues, camptothecine and gemcitabine), but also for immunotherapeutics and nucleic acids. Moreover, the alternative anticancer therapies based on thermal ablation and radiotherapy are discussed. The attention throughout the review is focused on the different targeting strategies proposed so far, mainly based on antibodies, but also on other specifically recognised molecules or on the application of an external magnetic field.     

Synergistically Enhanced Dispersion of Native Protein–Carbon Nanotube Conjugates by Fluoroalcohols in Aqueous Solution

Carbon nanotubes (CNTs) are anticipated as an important new material for use in nanotechnology applications because of their excellent mechanical and electrical properties. For their development, a highly stable dispersion of debundled CNTs is indispensable. Herein we present a new method to enhance dispersibility of single‐walled carbon nanotubes (SWNTs) with proteins using alcohols as co‐solvents. Addition of fluoroalcohols in solution increased the SWNT dispersion by more than one order of magnitude without protein denaturation. Enhancement of SWNT dispersion through addition of alcohols was attributed to the decreased hydrophobic interaction among SWNTs. This novel approach enables us to produce biofunctional CNTs such as one‐dimensional nanobiosensors and drug carriers that can penetrate cells.     

Non‐Covalent Functionalization of Carbon Nanotubes with Surfactants and Polymers

Carbon nanotubes (CNTs) possessing unique structure and properties are attractive building blocks for novel materials and devices of important practical interest. However, the insolubility or poor dispersibility of pristine CNTs in common solvents poses a serious obstacle to their further development. To effectively utilize CNTs as building blocks for nanotechnology, CNTs have been covalently and noncovalently functionalized in a number of ways to render them soluble in aqueous or organic solutions. Here, we review recent progress and advances that have been made on dispersion of carbon nanotubes in aqueous and organic media by non‐covalent functionalization with surfactants and polymers.     

Surface modified multi-walled carbon nanotubes in CNT/epoxy-composites

Multi-walled carbon nanotubes (MWCNTs), produced by arc-discharge method, were treated with oxidising inorganic acids. The surface modification of the oxidised nanotubes (o-MWCNTs) was achieved by refluxing the tubes with multi-functional amines. The functionalised nanotubes were embedded in the epoxy resin and the resulting composite was investigated by transmission-electron microscopy (TEM). The functionalisation led to a reduced agglomeration and evidences are given for improved interaction between the nanotubes and the epoxy resin.     

Selective Activation of a Prodrug by Thioredoxin Reductase Providing a Strategy to Target Cancer Cells

Elevated reactive oxygen species and antioxidant defense systems have been recognized as one of the hallmarks of cancer cells. As a major regulator of the cellular redox homeostasis, the selenoprotein thioredoxin reductase (TrxR) is increasingly considered as a promising target for anticancer drug development. The current approach to inhibit TrxR predominantly relies on the modification of the selenocysteine residue in the C‐terminal active site of the enzyme, in which it is hard to avoid the off‐target effects. By conjugating the anticancer drug gemcitabine with a 1,2‐dithiolane scaffold, an unprecedented prodrug strategy is disclosed that achieves a specific release of gemcitabine by TrxR in cells. As overexpression of TrxR is frequently found in different types of tumors, the TrxR‐dependent prodrugs are promising for further development as cancer chemotherapeutic agents.     

Antibody modified Bovine Serum Albumin microspheres for targeted delivery of anticancer agent Gemcitabine

Inhibition of the EGFR signaling pathway is one of the attractive therapeutic targets for pancreatic cancer as recent studies demonstrated that EGFR is over‐expressed in pancreatic cancer. In this article we have demonstrated the design of targeted drug delivery system containing Bovine Serum Albumin (BSA) microspheres as delivery vehicle, gemcitabine as anticancer drug and anti‐EGFR (epidermal growth factor receptor) monoclonal antibody as targeting agent. The conjugated BSA microspheres were characterized by several physico‐chemical techniques such as scanning electron microscope, optical microscopy, fluorescent microscopy etc. Administration of these BSA microspheres containing gemcitabine and anti‐EGFR (BSA‐Gem‐EGFR) shows significant inhibition of pancreatic cancer cells (AsPC1) compared to the cells treated with only BSA microspheres, BSA with gemcitabine (BSA‐Gem), and free gemcitabine. This strategy could be used as a generalized approach for the treatment of pancreatic cancer along with other cancers which overexpress EGFR on cell surface. Copyright © 2012 John Wiley & Sons, Ltd.     

Drug Conjugation to Cyclic Peptide–Polymer Self‐Assembling Nanotubes

We show for the first time how polymeric nanotubes (NTs) based on self‐assembled conjugates of polymers and cyclic peptides can be used as an efficient drug carrier. RAPTA‐C, a ruthenium‐based anticancer drug, was conjugated to a statistical co‐polymer based on poly(2‐hydroxyethyl acrylate) (pHEA) and poly(2‐chloroethyl methacrylate) (pCEMA), which formed the shell of the NTs. Self‐assembly into nanotubes (length 200–500 nm) led to structures exhibiting high activity against cancer cells.     

Doxorubicin Encapsulation in Carbon Nanotubes Having Haeckelite or Stone–Wales Defects as Drug Carriers: A Molecular Dynamics Approach

Doxorubicin (DOX), a recognized anticancer drug, forms stable associations with carbon nanotubes (CNTs). CNTs when properly functionalized have the ability to anchor directly in cancerous tumors where the release of the drug occurs thanks to the tumor slightly acidic pH. Herein, we study the armchair and zigzag CNTs with Stone–Wales (SW) defects to rank their ability to encapsulate DOX by determining the DOX-CNT binding free energies using the MM/PBSA and MM/GBSA methods implemented in AMBER16. We investigate also the chiral CNTs with haeckelite defects. Each haeckelite defect consists of a pair of square and octagonal rings. The armchair and zigzag CNT with SW defects and chiral nanotubes with haeckelite defects predict DOX-CNT interactions that depend on the length of the nanotube, the number of present defects and nitrogen doping. Chiral nanotubes having two haeckelite defects reveal a clear dependence on the nitrogen content with DOX-CNT interaction forces decreasing in the order 0N > 4N > 8N. These results contribute to a further understanding of drug-nanotube interactions and to the design of new drug delivery systems based on CNTs.     

The noble effect of aging on the thermal conductivity of modified CNTs-ethylene glycol nanofluids

In order to improve the heat transfer process by using nanofluids, different nanoparticles and base fluids have been studied. In this work, stability and effect of aging and temperature on the thermal conductivity of CNTs-ethylene glycol (EG) nanofluids were investigated. Chemical functionalisation was used to oxidise the surface of CNTs. The functionalised CNTs were used to prepare the nanofluids by a two-step method. The stability of nanofluids was measured by UV-vis spectroscopy and the results showed that the nanofluids had a good stability over several days. Immediately after nanofluid preparation not too much increase was observed for thermal conductivity but the nanofluid aging had a great influence on the improvement of the thermal conductivity, as after 65 days, about 50% increase was observed. The increase has been attributed to forming an ordered nanolayer of EG molecules around the CNTs. Also no significant temperature dependence of thermal conductivity was observed up to 50°C possibly due to the lack of temperature dependence of CNTs Brownian motions.     

Carbon nanotubes in emulsion‐templated porous polymers: Polymer nanoparticles,sulfonation, and conductivity

Sulfonated polymers are of interest for ion exchange resins, reaction supports, and membranes for separation, filtration, fuel cells, and electrochemical devices. Sulfonic groups have been introduced into polystyrene (PS) through exposure to sulfuric acid, and carbon nanotubes (CNTs) have been added to polymers to enhance proton conductivity without creating an electronic percolation pathway. PolyHIPEs, emulsion‐templated porous polymers with highly interconnected hierarchical open‐cell porous structures, are synthesized through polymerization in the external phases of high internal phase emulsions (HIPEs). In this article, the synthesis of PS‐based CNT‐filled polyHIPEs, their structure, sulfonation, and conductivity are described. Adding CNT dispersions to the HIPEs produced polymer nanoparticle–covered polyHIPEs from polymerization within the water‐soluble surfactant micelles in the internal aqueous phase droplets. The CNTs migrated from the HIPE's aqueous phase droplets into the HIPE's organic phase and formed interconnected bundles within the polyHIPE walls, reflecting a reduction in the surfactant's ability to disperse the CNTs. The water adsorption in the hygroscopic sulfonated polyHIPEs increased the conductivity by several orders of magnitude. The conductivity of the sulfonated polyHIPE containing CNTs was more than an order of magnitude greater than that of the sulfonated polyHIPEs with no CNTs. The CNTs act as “bridges,” enhancing the connection between existing conductive pathways. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4369–4377     

DFT study of SiO2 nanoparticles as a drug delivery system: structural and mechanistic aspects

Structural Chemistry - Adsorption and reaction mechanisms for the noncovalent and covalent functionalization of SiO2 nanoparticle (SiNP) with gemcitabine (GEM) anticancer drug have been...     

Characterisation of Nanohybrids of Porphyrins with Metallic and Semiconducting Carbon Nanotubes by EPR and Optical Spectroscopy

Single‐walled carbon nanotubes (SWCNTs) are noncovalently functionalised with octaethylporphyrins (OEPs) and the resulting nanohybrids are isolated from the free OEPs. Electron paramagnetic resonance (EPR) spectroscopy of cobalt(II)OEP, adsorbed on the nanotube walls by π–π‐stacking, demonstrates that the CNTs act as electron acceptors. EPR is shown to be very effective in resolving the different interactions for metallic and semiconducting tubes. Moreover, molecular oxygen is shown to bind selectively to nanohybrids with semiconducting tubes. Water solubilisation of the porphyrin/CNT nanohybrids using bile salts, after applying a thorough washing procedure, yields solutions in which at least 99 % of the porphyrins are interacting with the CNTs. Due to this purification, we observe, for the first time, the isolated absorption spectrum of the interacting porphyrins, which is strongly red‐shifted compared to the free porphyrin absorption. In addition a quasi‐complete quenching of the porphyrin fluorescence is also observed.     

Multivariate Modulation of the Zr MOF UiO‐66 for Defect‐Controlled Combination Anticancer Drug Delivery

Metal–organic frameworks (MOFs) are emerging as leading candidates for nanoscale drug delivery, as a consequence of their high drug capacities, ease of functionality, and the ability to carefully engineer key physical properties. Despite many anticancer treatment regimens consisting of a cocktail of different drugs, examples of delivery of multiple drugs from one MOF are rare, potentially hampered by difficulties in postsynthetic loading of more than one cargo molecule. Herein, we report a new strategy, multivariate modulation, which allows incorporation of up to three drugs in the Zr MOF UiO‐66 by defect‐loading. The drugs are added to one‐pot solvothermal synthesis and are distributed throughout the MOF at defect sites by coordination to the metal clusters. This tight binding comes with retention of crystallinity and porosity, allowing a fourth drug to be postsynthetically loaded into the MOFs to yield nanoparticles loaded with cocktails of drugs that show enhancements in selective anticancer cytotoxicity against MCF‐7 breast cancer cells in vitro. We believe that multivariate modulation is a significant advance in the application of MOFs in biomedicine, and anticipate the protocol will also be adopted in other areas of MOF chemistry, to easily produce defective MOFs with arrays of highly functionalised pores for potential application in gas separations and catalysis.     

Facile One‐Pot,One‐Step Synthesis of a Carbon Nanoarchitecture for an Advanced Multifunctonal Electrocatalyst

A one‐pot/one‐step synthesis strategy was developed for the preparation of a nitrogen‐doped carbon nanoarchitecture with graphene‐nanosheet growth on the inner surface of carbon nanotubes (CNTs). The N‐graphene/CNT hybrids exhibit outstanding electrocatalytic activity for several important electrochemical reactions as a result of their unique morphology and defect structures, such as high but uniform nitrogen doping, graphene insertion into CNTs, considerable surface area, and the presence of iron nanoparticles. The high‐yield synthetic process features high efficiency, low‐cost, straightforward operation, and simple equipment.     

Molecular dynamics assessment of doxorubicin–carbon nanotubes molecular interactions for the design of drug delivery systems

Carbon nanotubes (CNTs) constitute an interesting material for nanomedicine applications because of their unique properties, especially their ability to penetrate membranes, to transport drugs specifically and to be easily functionalized. In this work, the energies of the intermolecular interactions of single-walled CNTs and the anticancer drug doxorubicin (DOX) were determined using the AMBER 12 molecular dynamics MM/PBSA and MM/GBSA methods with the aim of better understanding how the structural parameters of the nanotube can improve the interactions with the drug and to determine which structural parameters are more important for increasing the stability of the complexes formed between the CNTs and DOX. The armchair, zigzag, and chiral nanotubes were finite hydrogen-terminated open tubes, and the DOX was encapsulated inside the tube or adsorbed on the nanotube surface. Pentagon/heptagon bumpy defects and polyethylene glycol (PEG) nanotube functionalization were also studied. The best interaction occurred when the drug was located inside the cavity of the nanotube. Armchair and zigzag nanotubes doped with nitrogen, favored interaction with the drug, whereas chiral nanotubes exhibited better drug interactions when having bumpy defects. The π-π stacking and N-H…π electrostatic interactions were important components of the attractive drug-nanotube forces, enabling significant flattening of the nanotube to favor a dual strong interaction with the encapsulated drug, with DOX–CNT equilibrium distances of 3.1–3.9 Å. These results can contribute to the modeling of new drug-nanotube delivery systems.

     

Density functional theory study on the possibility of Si‐, Ge‐, and Sn‐doped carbon nanotubes as efficient support materials for platinum

PBEPBE‐D3 calculations were performed to investigate how platinum (Pt) interacts with the internal and external surfaces of single‐walled pristine, Si‐, Ge‐, and Sn‐doped (6,6) carbon nanotubes (CNTs). Our calculations showed that atomic Pt demonstrates stronger binding strength on the external surfaces than the internal surface adsorption for the same type of nanotube. In cases of external surface adsorptions, Si‐, Ge‐, and Sn‐doped CNTs show comparable binding energies for Pt, at least 1.40 eV larger than pristine CNT. This enhancement can be rationalized by the strong covalent interactions between Pt and X? C (X = Si, Ge, and Sn) pairs based on structural and projected density of states analysis. In terms of internal surface adsorptions, Ge and Sn doping could significantly enhance the binding of Pt. Pt atom shows much more delocalized and bonding states inside Ge‐ and Sn‐doped CNTs, indicating multiple‐site interaction pattern when atomic Pt is confined inside the nanotubes. However, the internal surface of Si‐doped CNT presents limited enhancement in Pt adsorption with respect to that of pristine CNT because of their similar binding geometries. © 2016 Wiley Periodicals, Inc.