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Chemotherapy is a mainstay strategy in the management of cancer. Regrettably, current chemotherapeutic agents are cytotoxic not only to cancer cells but also to healthy cells, resulting in dose-limiting serious side effects. Therefore, many researchers are eager to develop new drug delivery systems that may help to decrease the side effects and the target delivery of chemotherapy to cancer cells. One of the epochal drug delivery systems in this field is based on carbon nanotubes technology. The aim of this work is the dual covalent functionalization of single-walled carbon nanotubes (SWCNTs) with doxorubicin (DOX) connected with acid-labile linkage and mannose (Man) as a targeting agent. The characterization of the developed nano-drug by transmission electron microscopy showed good dispersibility of the functionalized SWCNTs with diameters (6-10) nm. Moreover, the percentage of functionalization was determined by thermogravimetric analysis showing 25% of functionalization in the case of SWNCTs-NHN-DOX (7) and 51% for SWCNTs-Man-NHN-DOX (11). The in vitro release profile of Dox from SWNCTs-NHN-DOX (7) showed 45% of the loaded drug was released over 18 h at pH 7.4 and almost complete release at pH 6.4 at 37 °C. However, the in vitro release profile of Dox from SWCNTs-Man-NHN-DOX (11) showed 75% of the loaded drug was released over 5 h at pH 6.4 at 37 °C. The cytotoxic effect of the compounds was studied on liver cancer cells (HepG2) at different concentrations and different pH conditions and was compared with DOX alone. The cytotoxicity of compounds SWCNTs-NHN-DOX (7) and SWCNTs-Man-NHN-DOX (11) was enhanced at pH 6.5, where the cell viability in both test compounds was significantly reduced by almost 50% compared to the cell viability at pH 7.4 for the same test compound Moreover, the pre-incubation of cells with different concentrations of mannose reduced the cytotoxicity of compound (11) by more than 50%, suggesting that the entry of this complex could be at least in part facilitated by mannose receptors, which imparts this complex a kind of selectivity for cancer cells that overexpress this type of receptors.

Background: Bacterial resistance to antibiotics is one of the biggest challenges facing medicine today. Anti-adhesive therapy, using inhibitors of bacterial adhesion to epithelial cells, one of the first stages of infection, is a promising approximation in this area. The size, shape, number of sugar and their placement are variables that have to be taken into account in order to develop multivalent systems able to inhibit the bacterial adhesion based on sugar-lectin interaction., Materials and Methods: In the present work we report a modular approach for the synthesis of water-soluble 1D-carbon nanotube-sugar nanoconstructs, with the necessary flexibility to allow an efficient sugar-lectin interaction. The method is based on the reaction of aryl diazonium salts generated in situ from aniline-substituted mannose and lactose derivatives with single wall carbon nanotubes (SWCNTs) sidewalls., Results: Two hybrid nanosystems, I-II, exposing mannose or lactose and having a tetraethylene glycol spacer between the sugar and the nanotube sidewall were rapidly assembled and adequately characterized. The sweet nano-objects were then tested for their ability to agglutinate and selectively inhibit the growth of uropathogenic Escherichia coli . These studies have shown that nanosystem I, exposing mannose on the nanotube surface is able to agglutinate and to inhibit the bacterial growth unlike nano-objects II exposing lactose., Conclusion: The results reported constitute a proof of principle in using mannose-coated 1D-carbon nanotubes as antiadhesive drugs that compete for FimH binding and prevent the uropathogenic bacteria from adhering to the urothelial surface., Competing Interests: Disclosure ERB is recipient of an FPU PhD fellowship from the Spanish Ministry of Education, Culture and Sport. EF is recipient of a fellowship from the Junta de Andalucia (P11-CTS-7962/FEDER). The authors report no other conflicts of interest in this work.

To take full advantage of the remarkable applications of carbon nanotubes in different fields, there is a need to develop effective methods to improve their water dispersion and biocompatibility while maintaining their physical properties. In this sense, current approaches suffer from serious drawbacks such as loss of electronic structure together with low surface coverage in the case of covalent functionalizations, or instability of the dynamic hybrids obtained by non-covalent functionalizations. In the present work, we examined the molecular basis of an original strategy that combines the advantages of both functionalizations without their main drawbacks. The hierarchical self-assembly of diacetylenic-based neoglycolipids into highly organized and compacted rings around the nanotubes, followed by photopolymerization leads to the formation of nanotubes covered with glyconanorings with a shish kebab-type topology exposing the carbohydrate ligands to the water phase in a multivalent fashion. The glyconanotubes obtained are fully functional, and able to establish specific interactions with their cognate receptors. In fact, by taking advantage of this selective binding, an easy method to sense lectins as a working model of toxin detection was developed based on a simple analysis of TEM images. Remarkably, different experimental settings to assess cell membrane integrity, cell growth kinetics and cell cycle demonstrated the cellular biocompatibility of the sugar-coated carbon nanotubes compared to pristine single-walled carbon nanotubes.

We present a mild and practical carbon nanotubes rings (CNRs) synthesis from non-covalent functionalized and water-soluble linear single-wall carbon nanotubes. The hemi-micellar-supramolecular self-organization of lactose-based glycolipid 1 on the ring surface, followed by photo-polymerization of the diacetylenic function triggered by UV light afforded the first water-soluble and biocompatible CNRs. The obtained donut-like nanoconstructs expose a high density of lactose moieties on their surface, and are able to engage specific interactions with Arachis hypogea lectin similar to glycoconjugates on the cell membrane.

Remarkably stable, water-soluble glyconanoring-coated SWCNTs were prepared by self organization and photopolymerization of neutral diacetylene-based glycolipids on the nanotube surface; the nanoconstructs are able to engage in specific ligand-lectin interactions in a similar way to glycoconjugates on cell membranes.