Cellulose and chitin are the two most abundant natural polysaccharides. Both have a semicrystalline microfibrillar structure from which nanofibres can be extracted. These nanofibres are rod-like microcrystals that can be used as nanoscale reinforcements in composites due to their outstanding mechanical properties. This chapter starts by reviewing the sources, extraction methods and properties of cellulose and chitin nanofibres. Then, their use in the fabrication of structural and functional nanocomposites and the applications that have been investigated are reviewed. Nanocomposites are materials with internal nano-sized structures. They benefit from the properties of the nanofillers: low density, nonabrasive, nontoxic, low cost, susceptibility to chemical modifications and biodegradability. Diverse manufacturing technologies have been used to produce films, fibres, foams, sponges, aerogels, etc. Given their natural origin and high stiffness, these polymers have attracted a lot of attention not only in the biomedical and tissue engineering fields but also in areas such as pharmaceutics, cosmetics, agriculture, biosensors and water treatment.

Iron oxide nanoparticles (Fe3O4, IONPs) are promising candidates for several biomedical applications such as magnetic hyperthermia and as contrast agents for magnetic resonance imaging (MRI). However, their colloidal stability in physiological conditions hinders their application requiring the use of biocompatible surfactant agents. The present investigation focuses on obtaining highly stable IONPs, stabilized by the presence of an oleic acid bilayer. Critical aspects such as oleic acid concentration and pH were optimized to ensure maximum stability. NPs composed of an iron oxide core with an average diameter of 9 nm measured using transmission electron microscopy (TEM) form agglomerates with an hydrodynamic diameter of around 170 nm when dispersed in water in the presence of an oleic acid bilayer, remaining stable (zeta potential of −120 mV). Magnetic hyperthermia and the relaxivities measurements show high efficiency at neutral pH which enables their use for both magnetic hyperthermia and MRI.

Iron oxide nanoparticles (Fe3O4, IONPs) are promising candidates for several biomedical applications such as magnetic hyperthermia and as contrast agents for magnetic resonance imaging (MRI). However, their colloidal stability in physiological conditions hinders their application requiring the use of biocompatible surfactant agents. The present investigation focuses on obtaining highly stable IONPs, stabilized by the presence of an oleic acid bilayer. Critical aspects such as oleic acid concentration and pH were optimized to ensure maximum stability. NPs composed of an iron oxide core with an average diameter of 9 nm measured using transmission electron microscopy (TEM) form agglomerates with an hydrodynamic diameter of around 170 nm when dispersed in water in the presence of an oleic acid bilayer, remaining stable (zeta potential of −120 mV). Magnetic hyperthermia and the relaxivities measurements show high efficiency at neutral pH which enables their use for both magnetic hyperthermia and MRI.

The present study focus on the preparation of chromatography supports for affinity-based chromatography of supercoiled plasmid purification. Three l-tryptophan based supports are prepared through immobilization on epoxy-activated Sepharose and characterized by HR-MAS NMR. The SPR is employed for a fast screening of l-tryptophan derivatives, as potential ligands for the biorecognition of supercoiled isoform, as well as, to establish the suitable experimental conditions for the chromatography. The results reveal that the overall affinity is high (KD = 10−9 and 10−8 M) and the conditions tested show that the use of HEPES 100 mM enables the separation and purification of supercoiled at T = 10 °C. The STD-NMR is performed to accomplish the epitope mapping of the 5′-mononucleotides bound to l-tryptophan derivatives supports. The data shows that the interactions between the three supports and the 5′-mononucleotides are mainly hydrophobic and π–π stacking. The chromatography experiments are performed with l-tryptophan support and plasmids pVAX-LacZ and pPH600. The supercoiled isoform separation is achieved at T = 10 °C by decreasing the concentration of (NH4)2SO4 from 2.7 to 0 M in HEPES for pVAX-LacZ and 2.65 M to 0 M in HEPES for pPH600.

Overall, l-tryptophan derivatives can be a promising strategy to purify supercoiled for pharmaceutical applications.

PROPOSE:
Tin complexes demonstrate antiproliferative activities in some case higher than cisplatin, with IC50 at the low micromolar range. We have previously showed that the cyclic trinuclear complex of Sn(IV) bearing an aromatic oximehydroxamic acid group [nBu2Sn(L)]3 (L=N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) (MG85) shows high anti-proliferative activity, induces apoptosis and oxidative stress, and causes destabilization of tubulin microtubules, particularly in colorectal carcinoma cells. Despite the great efficacy towards cancer cells, this complex still shows some cytotoxicity to healthy cells. Targeted delivery of this complex specifically towards cancer cells might foster cancer treatment.
METHODS:
MG85 complex was encapsulated into liposomal formulation with and without an active targeting moiety and cancer and healthy cells cytotoxicity was evaluated.
RESULTS:
Encapsulation of MG85 complex in targeting PEGylated liposomes enhanced colorectal carcinoma (HCT116) cancer cell death when compared to free complex, whilst decreasing cytotoxicity in non-tumor cells. Labeling of liposomes with Rhodamine allowed assessing internalization in cells, which showed significant cell uptake after 6 h of incubation. Cetuximab was used as targeting moiety in the PEGylated liposomes that displayed higher internalization rate in HCT116 cells when compared with non-targeted liposomes, which seems to internalize via active binding of Cetuximab to cells.
CONCLUSIONS:
The proposed formulation open new avenues in the design of innovative transition metal-based vectorization systems that may be further extended to other novel metal complexes towards the improvement of their anti-cancer efficacy, which is usually hampered by solubility issues and/or toxicity to healthy tissues.

Phosphorylation is a reversible post-translational modification of proteins that controls a plethora of cellular processes and triggers specific physiological responses, for which there is a need to develop tools to characterize phosphorylated targets efficiently. Here, a combinatorial library of triazine-based synthetic ligands comprising 64 small molecules has been rationally designed, synthesized and screened for the enrichment of phosphorylated peptides. The lead candidate (coined A8A3), composed of histidine and phenylalanine mimetic components, showed high binding capacity and selectivity for binding mono- and multi-phosphorylated peptides at pH 3. Ligand A8A3 was coupled onto both cross-linked agarose and magnetic nanoparticles, presenting higher binding capacities (100-fold higher) when immobilized on the magnetic support. The magnetic adsorbent was further screened against a tryptic digest of two phosphorylated proteins ($\alpha$- and $\beta$-caseins) and one non-phosphorylated protein (bovine serum albumin, BSA). The MALDI-TOF mass spectra of the eluted peptides allowed the identification of nine phosphopeptides, comprising both mono- and multi-phosphorylated peptides.

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Cellulose and chitin are the two most abundant natural polysaccharides. Both have a semicrystalline microfibrillar structure from which nanofibres can be extracted. These nanofibres are rod-like microcrystals that can be used as nanoscale reinforcements in composites due to their outstanding mechanical properties. This chapter starts by reviewing the sources, extraction methods and properties of cellulose and chitin nanofibres. Then, their use in the fabrication of structural and functional nanocomposites and the applications that have been investigated are reviewed. Nanocomposites are materials with internal nano-sized structures. They benefit from the properties of the nanofillers: low density, nonabrasive, nontoxic, low cost, susceptibility to chemical modifications and biodegradability. Diverse manufacturing technologies have been used to produce films, fibres, foams, sponges, aerogels, etc. Given their natural origin and high stiffness, these polymers have attracted a lot of attention not only in the biomedical and tissue engineering fields but also in areas such as pharmaceutics, cosmetics, agriculture, biosensors and water treatment.

Fresh-cut fruit is an important segment in fruit market due to the increasing demand for healthy/convenient foods. However, processing promotes a decrease in fruits stability with faster physiological and microbiological deteriorations. Food stability is strongly attributed to its molecular dynamics and “water availability”. Understanding changes in water location/mobility is of utmost importance, since water dynamics profoundly influences physic-chemical and microbiological quality of foods. Nuclear magnetic resonance spectroscopy (NMR) is a methodology used to study the food constituents' molecular dynamics.

The aim of this study is to use NMR to evaluate changes in water mobility that occurred in fresh-cut pear tissues during storage, by measuring the transverse relaxation time (T2) parameter.

Results showed the existence of three water classes in the cells after processing, with T2 values of 10 ms, 187 ms and 3s for cellular wall, cytoplasm and vacuole, respectively. Also, the obtained results demonstrated that T2 was affected by processing and storage. Moreover, a relationship between T2, microstructure and the quality parameters was established. T2, maximum value increased with pear hardness as well as water activity. On the contrary, a decrease in total colour difference (TCD) was found with T2.

Results demonstrate the usefulness of the application of NMR relaxometry in food studies.

Lung cancer is the leading cause of cancer-related mortality in the world, non-small lung cancer (NSCLC) is the most frequent subtype (85% of the cases). Within this subtype, adenocarcinoma and squamous cell carcinoma are the most frequent. New therapeutic strategies based on targeted delivery of drugs have relied on the use of biomarkers derived from the patients’ molecular profiling. Several biomarkers have been found to be useful for use as targets for precision therapy in NSCLC, such as mutations in the epidermal growth factor receptor, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, anaplastic lymphoma kinase, mesenchymal-epithelial transition factor receptor tyrosine kinase, BRAF, c-ros oncogene 1, P53 and phosphatase with tensin homology. Current developments in Nanomedicine have allowed for multifunctional systems capable of delivering therapeutics with increased precision to the target site/tissue, while simultaneously assisting in diagnosis. Here, we review the use of biomarkers in nanotechnology translation in NSCLC management.

The first lanthanopolyoxometalate-supported bifunctional periodic mesoporous organosilica (BPMO) composite is here reported. The incorporation of decatunsgstoeuropate anions ([Eu(W5O18)2]9−) within the porous channels of an ethylene-bridged TMAPS-functionalized BPMO produced a luminescent material exhibiting a strong red emission under UV irradiation. Photoluminescence studies showed an efficient energy transfer process to the lanthanide emitting center in the material (antenna effect). A significant change in the coordination environment of Eu3+ ions was observed after its incorporation into the TMAPS-functionalized material. The possible reason for this is discussed within the paper.

The PVT1 lncRNA has recently been involved in tumorigenesis by affecting the protein stability of the MYC proto-oncogene. Both MYC and PVT1 reside in a well-known cancer-risk locus and enhanced levels of their products have been reported in different human cancers. Nonetheless, the extension and relevance of the MYC-PVT1 deregulation in tumorigenesis has not yet been systematically addressed.Here we performed a pan-cancer analysis of matched copy number, transcriptomic, methylation, proteomic and clinicopathological profiles for almost 7000 patients from 17 different cancers represented in the TCGA cohorts. Among all cancers types, kidney renal clear cell carcinoma (KIRC) showed the strongest upregulation of PVT1 and increased levels of both MYC and PVT1 correlated with the clinical outcome. PVT1 misregulation in KIRC is mostly associated to promoter hypomethylation rather than locus amplification. Furthermore, we found an association between MYC levels and PVT1 expression, which impacted on MYC-target genes.Collectively, our study discloses the role of PVT1 as a novel prognostic factor and as a molecular target for novel therapeutic interventions in renal carcinoma.

In this work, peptides designed to selectively interact with cellular receptors involved in the regulation of angiogenesis were anchored to oligo-ethylene glycol-capped gold nanoparticles (AuNPs) and used to evaluate the modulation of vascular development using an ex ovo chick chorioallantoic membrane assay. These nanoparticles alter the balance between naturally secreted pro- and antiangiogenic factors, under various biological conditions, without causing toxicity. Exposure of chorioallantoic membranes to AuNP–peptide activators of angiogenesis accelerated the formation of new arterioles when compared to scrambled peptide-coated nanoparticles. On the other hand, antiangiogenic AuNP–peptide conjugates were able to selectively inhibit angiogenesis in vivo. We demonstrated that AuNP vectorization is crucial for enhancing the effect of active peptides. Our data showed for the first time the effective control of activation or inhibition of blood vessel formation in chick embryo via AuNP-based formulations suitable for the selective modulation of angiogenesis, which is of paramount importance in applications where promotion of vascular growth is desirable (eg, wound healing) or ought to be contravened, as in cancer development.

Affinity chromatography is a widespread technique for the enrichment and isolation of biologics, which relies on the selective and reversible interaction between affinity ligands and target molecules. Small synthetic affinity ligands are valuable alternatives due to their robustness, low cost and fast ligand development. This work reports, for the first time, the use of a sequential Petasis-Ugi multicomponent reaction to generate rationally designed solid-phase combinatorial libraries of small synthetic ligands, which can be screened for the selection of new affinity adsorbents towards biological targets. As a proof of concept, the Petasis-Ugi reaction was here employed in the discovery of affinity ligands suitable for phosphopeptide enrichment. A combinatorial library of 84 ligands was designed, synthesized on a chromatographic solid support and screened in situ for the specific binding of phosphopeptides binding human BRCA1C-terminal domains. The success of the reaction on the chromatographic matrix was confirmed by both inductively coupled plasma atomic emission spectroscopy and fluorescence microscopy. Three lead ligands were identified due to their superior performance in terms of binding capacity and selectivity towards the phosphorylated moiety on peptides, which showed the feasibility of the Petasis-Ugi reaction for affinity ligand development.

Magnetic nanocomposites are hybrid structures consisting of an iron oxide (Fe3O4 /$\gamma$-Fe2O3 ) superparamagnetic core and a coating shell which presents affi nity for a specifi c target molecule. Within the scope of phosphopeptide enrichment, the magnetic core is usually fi rst functionalized with an intermediate layer of silica or carbon to improve dispersibility and increase specifi c area, and then with an outer layer of a phosphate-affi nity material. Fe3O4 -coating materials include metal oxides, rare earth metal-based compounds, immobilized-metal ions, polymers, and many others. This chapter provides a generic overview of the different materials that can be found in literature and their advantages and drawbacks.