Cu(I) Coordination Compounds Conjugated to Au Nanorods for Future Applications in Drug Delivery: Insights in Molecular, Electronic and Cu Local Structure in Solid and Liquid Phase.

In the framework of the design, synthesis and testing of a library of copper complexes and nanostructured assemblies potentially endowed with antitumor and antiviral activity and useful for several applications, from drugs and related delivery systems to the development of biocidal nanomaterials, we present the detailed spectroscopic investigation of the molecular and electronic structure of copper-based coordination compounds and of a new conjugated system obtained by grafting Cu(I) complexes to gold nanorods. More in detail, the electronic and molecular structures of two Cu complexes and one AuNRs/Cu-complex adduct were investigated by X-ray photoelectron spectroscopy (XPS), synchrotron-induced XPS (SR-XPS) and near edge X-ray absorption spectroscopy (NEXAFS) in solid state, and the local structure around copper ion was assessed by X-ray absorption spectroscopy (XAS) both in solid state and water solution for the AuNRs/Cu-complex nanoparticles. The proposed multi-technique approach allowed to properly define the coordination geometry around the copper ion, as well as to ascertain the molecular structures of the coordination compounds, their stability and modifications upon interaction with gold nanoparticles, by comparing solid state and liquid phase data.

Multifunctional Platform for Covalent Titanium Coatings: Micro-FTIR, XPS, and NEXAFS Characterizations.

This work aims at preparing and characterizing a versatile multifunctional platform enabling the immobilization of macromolecules on a titanium surface by robust covalent grafting. Functionalized titanium is widely used in the biomedical field to improve its properties. Despite its high biocompatibility and osteointegrability, titanium implants are not very stable in the long term due to the onset of inflammation and bacterial infections. The proposed method allows the superficial insertion of three different organic linkers to be used as anchors for the attachment of biopolymers or bioactive molecules. This strategy used green solvents and is a good alternative to the proposed classic methods that employ organic solvents. The uniformly modified surfaces were characterized by micro-Fourier transform infrared spectroscopy (micro-FTIR), X-ray Photoelectron spectroscopy (XPS) and Near-Edge X-ray Absorption Fine Structure (NEXAFS). The latter made it possible to assess the orientation of the linker molecules with respect to the titanium surface. To test the efficiency of the linkers, two polymers (alginate and 2-(dimethylamino)-ethyl methacrylate (PDMAEMA)), with the potential ability to increase biocompatibility, were covalently attached to the titanium surfaces. The obtained results are a good starting point for the realization of stable polymeric coatings permanently bonded to the surface that could be used to extend the life of biomedical implants.

A Novel Resveratrol-Induced Pathway Increases Neuron-Derived Cell Resilience against Oxidative Stress.

A promising therapeutic strategy to delay and/or prevent the onset of neurodegenerative diseases (NDs) could be to restore neuroprotective pathways physiologically triggered by neurons against stress injury. Recently, we identified the accumulation of neuroglobin (NGB) in neuronal cells, induced by the 17ß-estradiol (E2)/estrogen receptor ß (ERß) axis, as a protective response that increases mitochondria functionality and prevents the activation of apoptosis, increasing neuron resilience against oxidative stress. Here, we would verify if resveratrol (Res), an ERß ligand, could reactivate NGB accumulation and its protective effects against oxidative stress in neuronal-derived cells (i.e., SH-SY5Y cells). Our results demonstrate that ERß/NGB is a novel pathway triggered by low Res concentrations that lead to rapid and persistent NGB accumulation in the cytosol and in mitochondria, where the protein contributes to reducing the apoptotic death induced by hydrogen peroxide (H2O2). Intriguingly, Res conjugation with gold nanoparticles increases the stilbene efficacy in enhancing neuron resilience against oxidative stress. As a whole, ERß/NGB axis regulation is a novel mechanism triggered by low concentration of Res to regulate, specifically, the neuronal cell resilience against oxidative stress reducing the triggering of the apoptotic cascade.

Resveratrol Analogs and Prodrugs Differently Affect the Survival of Breast Cancer Cells Impairing Estrogen/Estrogen Receptor α/Neuroglobin Pathway.

Breast cancer is the first leading tumor in women in terms of incidence worldwide. Seventy percent of cases are estrogen receptor (ER) α-positive. In these malignancies, 17ß-estradiol (E2) via ERα increases the levels of neuroglobin (NGB), a compensatory protein that protects cancer cells from stress-induced apoptosis, including chemotherapeutic drug treatment. Our previous data indicate that resveratrol (RSV), a plant-derived polyphenol, prevents E2/ERα-induced NGB accumulation in this cellular context, making E2-dependent breast cancer cells more prone to apoptosis. Unfortunately, RSV is readily metabolized, thus preventing its effectiveness. Here, four different RSV analogs have been developed, and their effect on the ERα/NGB pathway has been compared with RSV conjugated with highly hydrophilic gold nanoparticles as prodrug to evaluate if RSV derivatives maintain the breast cancer cells' susceptibility to the chemotherapeutic drug paclitaxel as the original compound. Results demonstrate that RSV conjugation with gold nanoparticles increases RSV efficacy, with respect to RSV analogues, reducing NGB levels and enhancing the pro-apoptotic action of paclitaxel, even preventing the anti-apoptotic action exerted by E2 treatment on these cells. Overall, RSV conjugation with gold nanoparticles makes this complex a promising agent for medical application in breast cancer treatment.

Cu(I) and Cu(II) Complexes Based on Lonidamine-Conjugated Ligands Designed to Promote Synergistic Antitumor Effects.

Bis(pyrazol-1-yl)- and bis(3,5-dimethylpyrazol-1-yl)-acetates were conjugated with the 2-hydroxyethylester and 2-aminoethylamide derivatives of the antineoplastic drug lonidamine to prepare Cu(I) and Cu(II) complexes that might act through synergistic mechanisms of action due to the presence of lonidamine and copper in the same chemical entity. Synchrotron radiation-based complementary techniques [X-ray photorlectron spectroscopy and near-edge X-ray absorption fine structure (NEXAFS)] were used to characterize the electronic and molecular structures of the complexes and the local structure around the copper ion (XAFS) in selected complexes. All complexes showed significant antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human tumor cell lines, and were able to overcome oxaliplatin and multidrug resistance. Noticeably, these Cu complexes appeared much more effective than cisplatin against 3D spheroids of pancreatic PSN-1 cancer cells; among these, PPh3-containing Cu(I) complex 15 appeared to be the most promising derivative. Mechanistic studies revealed that 15 induced cancer cell death by means of an apoptosis-alternative cell death.

Pterostilbene fluorescent probes as potential tools for targeting neurodegeneration in biological applications.

Several epidemiological studies suggest that a diet rich in fruit and vegetables reduces the incidence of neurodegenerative diseases. Resveratrol (Res) and its dimethylated metabolite, pterostibene (Ptb), have been largely studied for their neuroprotective action. The clinical use of Res is limited because of its rapid metabolism and its poor bioavailability. Ptb with two methoxy groups and one hydroxyl group has a good membrane permeability, metabolic stability and higher in vivo bioavailability in comparison with Res. The metabolism and pharmacokinetics of Ptb are still sparse, probably due to the lack of tools that allow following the Ptb destiny both in living cells and in vivo. In this contest, we propose two Ptb fluorescent derivatives where Ptb has been functionalised by benzofurazan and rhodamine-B-isothiocyanate, compounds 1 and 2, respectively. Here, we report the synthesis, the optical and structural characterisation of 1 and 2, and, their putative cytotoxicity in two different cell lines.

Exploring the Antitumor Potential of Copper Complexes Based on Ester Derivatives of Bis(pyrazol-1-yl)acetate Ligands.

Bis(pyrazol-1-yl)acetic acid (HC(pz)2COOH) and bis(3,5-dimethyl-pyrazol-1-yl)acetic acid (HC(pzMe2)2COOH) were converted into the methyl ester derivatives 1 (LOMe) and 2 (L2OMe), respectively, and were used for the preparation of Cu(I) and Cu(II) complexes 3-10. The copper(II) complexes were prepared by the reaction of CuCl2·2H2O or CuBr2 with ligands 1 and 2 in methanol solution. The copper(I) complexes were prepared by the reaction of Cu[(CH3CN)4]PF6 and 1,3,5-triaza-7-phosphaadamantane (PTA) or triphenylphosphine with LOMe and L2OMe in acetonitrile solution. Synchrotron radiation-based complementary techniques (XPS, NEXAFS, and XAS) were used to investigate the electronic and molecular structures of the complexes and the local structure around copper ions in selected Cu(I) and Cu(II) coordination compounds. All Cu(I) and Cu(II) complexes showed a significant in vitro antitumor activity, proving to be more effective than the reference drug cisplatin in a panel of human cancer cell lines, and were able to overcome cisplatin resistance. Noticeably, Cu complexes appeared much more effective than cisplatin in 3D spheroid cultures. Mechanistic studies revealed that the antitumor potential did not correlate with cellular accumulation but was consistent with intracellular targeting of PDI, ER stress, and paraptotic cell death induction.

Bio-Functionalized Chitosan for Bone Tissue Engineering.

Hybrid biomaterials allow for the improvement of the biological properties of materials and have been successfully used for implantology in medical applications. The covalent and selective functionalization of materials with bioactive peptides provides favorable results in tissue engineering by supporting cell attachment to the biomaterial through biochemical cues and interaction with membrane receptors. Since the functionalization with bioactive peptides may alter the chemical and physical properties of the biomaterials, in this study we characterized the biological responses of differently functionalized chitosan analogs. Chitosan analogs were produced through the reaction of GRGDSPK (RGD) or FRHRNRKGY (HVP) sequences, both carrying an aldehyde-terminal group, to chitosan. The bio-functionalized polysaccharides, pure or "diluted" with chitosan, were chemically characterized in depth and evaluated for their antimicrobial activities and biocompatibility toward human primary osteoblast cells. The results obtained indicate that the bio-functionalization of chitosan increases human-osteoblast adhesion (p < 0.005) and proliferation (p < 0.005) as compared with chitosan. Overall, the 1:1 mixture of HVP functionalized-chitosan:chitosan is the best compromise between preserving the antibacterial properties of the material and supporting osteoblast differentiation and calcium deposition (p < 0.005 vs. RGD). In conclusion, our results reported that a selected concentration of HVP supported the biomimetic potential of functionalized chitosan better than RGD and preserved the antibacterial properties of chitosan.

Cysteine-Modified Self-Assembling Peptides on Gold: The Role of the Head and Tail.

Molecular self-assembly consists of the spontaneous aggregation of molecules into a well-defined structure guided by noncovalent bonds. The self-assembly strategy is ubiquitous in nature and recently has been proposed as a nature-mimetic strategy in polymer science and biomaterial engineering. In this context, we aim at designing and testing innovative but simple chemical strategies to efficiently modify surfaces by exploiting minor modifications in the bioactive molecule functionalities, for example, introducing cysteine (Cys) as a terminal residue in self-assembling peptides (SAPs). In this work, we report the attenuated total reflection-Fourier transform infrared spectroscopy, synchrotron radiation-induced X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, and time-of-flight secondary ion mass spectrometry investigation of self-assembled layers of oligopeptides anchored onto gold surfaces through cysteine residues, opportunely inserted in an SAP (EAK16-II) main chain in three different positions: at the amine end group, at the carboxyl end group, and at both terminal groups (i.e., a bidentate SAP). This study, which allowed us to individuate in the bidentate SAP the best candidate for the controlled production of ordered SAP layers on the gold substrate surface, is envisaged to open wide perspectives for efficient chemical modification of surfaces with biomolecules, leading to obtaining innovative bioactive materials for applications in the field of tissue engineering.

Gallium- and Iron-Pyoverdine Coordination Compounds Investigated by X-ray Photoelectron Spectroscopy and X-ray Absorption Spectroscopy.

Iron is an essential nutrient for nearly all forms of life, although scarcely available due to its poor solubility in nature and complex formation in higher eukaryotes. Microorganisms have evolved a vast array of strategies to acquire iron, the most common being the production of high-affinity iron chelators, termed siderophores. The opportunistic bacterial pathogen Pseudomonas aeruginosa synthesizes and secretes two siderophores, pyoverdine (PVD) and pyochelin (PCH), characterized by very different structural and functional properties. Due to its chemical similarity with Fe(III), Ga(III) interferes with several iron-dependent biological pathways. Both PVD and PCH bind Fe(III) and Ga(III). However, while the Ga-PCH complex is more effective than Ga(III) in inhibiting P. aeruginosa growth, PVD acts as a Ga(III) scavenger and protects bacteria from Ga(III) toxicity. To gain more insight into the different outcomes of the biological paths observed for the Fe(III) and Ga(III)-siderophore complexes, better knowledge is needed of their coordination geometries that directly influence the metal complexes chemical stability. The valence state and coordination geometry of the Ga-PCH and Fe-PCH complexes has recently been investigated in detail; as for PVD complexes, several NMR structural studies of Ga(III)-PVD are reported in the literature, using Ga(III) as a diamagnetic isosteric substitute for Fe(III). In this work, we applied up-to-date spectroscopic techniques as synchrotron-radiation-induced X-ray photoelectron spectroscopy (SR-XPS) and X-ray absorption fine structure (XAFS) spectroscopy coupled with molecular modeling to describe the electronic structure and coordination chemistry of Fe and Ga coordinative sites in PVD metal complexes. These techniques allowed us to unambiguously determine the oxidation state of the coordinative ions and to gather interesting information about the similarities and differences between the two coordination compounds as induced by the different metal.

Facile and selective covalent grafting of an RGD-peptide to electrospun scaffolds improves HUVEC adhesion.

The development of a biomimetic surface able to promote endothelialization is fundamental in the search for blood vessel substitutes that prevent the formation of thrombi or hyperplasia. This study aims at investigating the effect of functionalization of poly-ε-caprolactone or poly(L-lactic acid-co-ɛ-caprolactone) electrospun scaffolds with a photoreactive adhesive peptide. The designed peptide sequence contains four Gly-Arg-Gly-Asp-Ser-Pro motifs per chain and a p-azido-Phe residue at each terminus. Different peptide densities on the scaffold surface were obtained by simply modifying the peptide concentration used in pretreatment of the scaffold before UV irradiation. Scaffolds of poly-ε-caprolactone embedded with adhesive peptides were produced to assess the importance of peptide covalent grafting. Our results show that the scaffolds functionalized with photoreactive peptides enhance adhesion at 24 h with a dose-dependent effect and control the proliferation of human umbilical vein endothelial cells, whereas the inclusion of adhesive peptide in the electrospun matrices by embedding does not give satisfactory results.

Three-Dimensional Printed Filters Based on Poly(ethylene glycol) Diacrylate Hydrogels Doped with Silver Nanoparticles for Removing Hg(II) Ions from Water.

Nowadays, due to water pollution, more and more living beings are exposed to dangerous compounds, which can lead to them contracting diseases. The removal of contaminants (including heavy metals) from water is, therefore, a necessary aspect to guarantee the well-being of living beings. Among the most used techniques, the employment of adsorbent materials is certainly advantageous, as they are easy to synthesize and are cheap. In this work, poly(ethylene glycol) diacrylate (PEGDA) hydrogels doped with silver nanoparticles (AgNPs) for removing Hg(II) ions from water are presented. AgNPs were embedded in PEGDA-based matrices by using a photo-polymerizable solution. By exploiting a custom-made 3D printer, the filters were synthesized. The kinetics of interaction was studied, revealing that the adsorption equilibrium is achieved in 8 h. Subsequently, the adsorption isotherms of PEGDA doped with AgNPs towards Hg(II) ions were studied at different temperatures (4 °C, 25 °C, and 50 °C). In all cases, the best isotherm model was the Langmuir one (revealing that the chemisorption is the driving process and the most favorable one), with maximum adsorption capacities equal to 0.55, 0.57, and 0.61 mg/g, respectively. Finally, the removal efficiency was evaluated for the three temperatures, obtaining for 4 °C, 25 °C, and 50 °C the values 94%, 94%, and 86%, respectively.

Silver Nanoparticles Supported onto TEMPO-Oxidized Cellulose Nanofibers for Promoting Cd2+ Cation Adsorption.

Nanocellulose constitutes a sustainable and biobased solution both as an efficient sorbent material for water treatment and as support for other inorganic nanomaterials with sorbent properties. Herein, we report the synthesis of a nanocomposite by deposition of in situ-generated silver nanoparticles (AgNPs) onto TEMPO-oxidized cellulose nanofibers (TOCNFs). Following an in-depth analytical investigation, we unveil for the first time the key role of AgNPs in enhancing the adsorption efficiency of TOCNF toward Cd2+ ions, chosen as model heavy metal contaminants. The obtained nanocomposite shows a value of Cd2+ sorption capacity at equilibrium from 150 mg L-1 ion aqueous solutions of ∼116 mg g-1 against the value of 78 mg g-1 measured for TOCNF alone. A combination of field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray (EDX), and X-ray photoelectron spectroscopy (XPS) analyses suggests that Cd2+ ions are mainly adsorbed in the neighborhood of AgNPs. However, XPS characterization allows us to conclude that the role of AgNPs relies on increasing the exposure of carboxylic groups with respect to the original TOCNF, suggesting that these groups are still responsible for absorption. In fact, X-ray absorption spectroscopy (XAS) analysis of the Cd-K edge excludes a direct interaction between Ag0 and Cd2+, supporting the XPS results and confirming the coordination of the latter with carboxyl groups.

Resorbable engineered barrier membranes for oral surgery applications.

Population aging, reduced economic capacity, and neglecting the treatments for oral pathologies, are the main causal factors for about 3 billion individuals who are suffering from partial/total edentulism or alveolar bone resorption: thus, the demand for dental implants is increasingly growing. To achieve a good prognosis for implant-supported restorations, adequate peri-implant bone volume is mandatory. The Guided Bone Regeneration (GBR) technique is one of the most applied methods for alveolar bone reconstruction and treatment of peri-implant bone deficiencies. This technique involves the use of different types of membranes in association with some bone substitutes (autologous, homologous, or heterologous). However, time for bone regeneration is often too long and the bone quality is not simply predictable. This study aims at engineering and evaluating the efficacy of modified barrier membranes, enhancing their bioactivity for improved alveolar bone tissue regeneration. We investigated membranes functionalized with chitosan (CS) and chitosan combined with the peptide GBMP1α (CS + GBMP1α), to improve bone growth. OsseoGuard® membranes, derived from bovine Achilles tendon type I collagen crosslinked with formaldehyde, were modified using CS and CS + GBMP1α. The functionalization, carried out with 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide and sulfo-N-Hydroxysuccinimide (EDC/sulfo-NHS), was assessed through FT-IR and XPS analyses. Biological assays were performed by directly seeding human osteoblasts onto the materials to assess cell proliferation, mineralization, gene expression of Secreted Phosphoprotein 1 (SPP1) and Runt-Related Transcription Factor 2 (Runx2), and antibacterial properties. Both CS and CS + GBMP1α functionalizations significantly enhanced human osteoblast proliferation, mineralization, gene expression, and antibacterial activity compared to commercial membranes. The CS + GBMP1α functionalization exhibited superior outcomes in all biological assays. Mechanical tests showed no significant alterations of membrane biomechanical properties post-functionalization. The engineered membranes, especially those functionalized with CS + GBMP1α, are suitable for GBR applications thanks to their ability to enhance osteoblast activity and promote bone tissue regeneration. These findings suggest a potential advancement in the treatment of oral cavity problems requiring bone regeneration.

Copper-Based Complexes with Adamantane Ring-Conjugated bis(3,5-Dimethyl-pyrazol-1-yl)acetate Ligand as Promising Agents for the Treatment of Glioblastoma.

The new ligand L2Ad, obtained by conjugating the bifunctional species bis(3,5-dimethylpyrazol-1-yl)-acetate and the drug amantadine, was used as a chelator for the synthesis of new Cu complexes 1-5. Their structures were investigated by synchrotron radiation-induced X-ray photoelectron spectroscopy (SR-XPS), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, and by combining X-ray absorption fine structure (XAFS) spectroscopy techniques and DFT modeling. The structure of complex 3 was determined by single-crystal X-ray diffraction analysis. Tested on U87, T98, and U251 glioma cells, Cu(II) complex 3 and Cu(I) complex 5 decreased cell viability with IC50 values significantly lower than cisplatin, affecting cell growth, proliferation, and death. Their effects were prevented by treatment with the Cu chelator tetrathiomolybdate, suggesting the involvement of copper in their cytotoxic activity. Both complexes were able to increase ROS production, leading to DNA damage and death. Interestingly, nontoxic doses of 3 or 5 enhanced the chemosensitivity to Temozolomide.

Gold nanorods derivatized with CTAB and hydroquinone or ascorbic acid: spectroscopic investigation of anisotropic nanoparticles of different shapes and sizes.

Gold nanorods stabilized by binary ligand mixtures of cetyltrimethylammonium bromide (CTAB, primary ligand) and ascorbic acid or hydroquinone were investigated by complementary synchrotron radiation-induced spectroscopies and microscopies, with the aim to find evidence of the influence of the secondary ligand molecular and chemical structure on the nanorod shapes and size ratios. Indeed, as it is well known that the CTAB interaction with Ag(i) ions at the NR surface plays a key role in directing the anisotropic growth of nanorods, the possibility to finely control the NR shape and dimension by opportunely selecting the secondary ligands opens new perspectives in the design and synthesis of anisotropic nanoparticles.

Dye-Doped Polymeric Microplastics: Light Tools for Bioimaging in Test Organisms.

Ecosystems around the world are experiencing a major environmental impact from microplastic particles (MPs 0.1 µm-1 mm). Water, sediments, and aquatic biota show the widespread presence of this pollutant. However, MPs are rarely used in laboratory studies as they are scarcely available for purchase or expensive, especially if one wishes to trace the particle with a dye or fluorescent. Furthermore, existing preparation techniques have limited application in biological studies. In this work, we propose a new, easy, and cheap way to prepare fluorescent MPs. The protocol is based on the osmosis method in order to obtain spherical polymeric particles of P(S-co-MMA), with 0.7-9 micron diameter, made fluorescent because dye-doped with rhodamine B isothiocyanate (RITC) or fluorescein isothiocyanate (FITC). The dye loading was studied and optimized, and the MPs-dye conjugates were characterized by UV-vis FTIR and XPS spectrometry and scanning electron microscopy (SEM). Furthermore, preliminary tests on aquatic organisms demonstrated the possible use of these fluorescent MPs in bioimaging studies, showing their absorption/adsorption by duckweeds (Lemna minuta) and insect larvae (Cataclysta lemnata).

Bioactive PEEK: Surface Enrichment of Vitronectin-Derived Adhesive Peptides.

Polyetheretherketone (PEEK) is a thermoplastic polymer that has been recently employed for bone tissue engineering as a result of its biocompatibility and mechanical properties being comparable to human bone. PEEK, however, is a bio-inert material and, when implanted, does not interact with the host tissues, resulting in poor integration. In this work, the surfaces of 3D-printed PEEK disks were functionalized with: (i) an adhesive peptide reproducing [351-359] h-Vitronectin sequence (HVP) and (ii) HVP retro-inverted dimer (D2HVP), that combines the bioactivity of the native sequence (HVP) with the stability toward proteolytic degradation. Both sequences were designed to be anchored to the polymer surface through specific covalent bonds via oxime chemistry. All functionalized PEEK samples were characterized by Water Contact Angle (WCA) measurements, Atomic Force Microscopy (AFM), and X-ray Photoelectron Spectroscopy (XPS) to confirm the peptide enrichment. The biological results showed that both peptides were able to increase cell proliferation at 3 and 21 days. D2HVP functionalized PEEK resulted in an enhanced proliferation across all time points investigated with higher calcium deposition and more elongated cell morphology.

Gold Nanorods as Radiopharmaceutical Carriers: Preparation and Preliminary Radiobiological In Vitro Tests.

Low-energy electrons (Auger electrons) can be produced via the interaction of photons with gold atoms in gold nanorods (AuNRs). These electrons are similar to those emitted during the decay of technetium-99m (99mTc), a radioactive nuclide widely used for diagnostics in nuclear medicine. Auger and internal conversion (IC) electron emitters appropriately targeted to the DNA of tumors cells may, therefore, represent a new radiotherapeutic approach. 99mTc radiopharmaceuticals, which are used for diagnosis, could indeed be used in theragnostic fields when loaded on AuNRs and delivered to a tumor site. This work aims to provide a proof of concept (i) to evaluate AuNRs as carriers of 99mTc-based radiopharmaceuticals, and (ii) to evaluate the efficacy of Auger electrons emitted by photon-irradiated AuNRs in inducing radio-induced damage in T98G cells, thus mimicking the effect of Auger electrons emitted during the decay of 99mTc used in clinical settings. Data are presented on AuNRs' chemical characterization (with an aspect ratio of 3.2 and Surface Plasmon Resonance bands at 520 and 680 nm) and the loading of pharmaceuticals (after 99mTc decay) on their surface. Spectroscopic characterizations, such as UV-Vis and synchrotron radiation-induced X-ray photoelectron (SR-XPS) spectroscopies, were performed to investigate the drug-AuNR interaction. Finally, preliminary radiobiological data on cell killing with AuNRs are presented.

Strategies for the Covalent Anchoring of a BMP-2-Mimetic Peptide to PEEK Surface for Bone Tissue Engineering.

Researchers in the field of tissue engineering are always searching for new scaffolds for bone repair. Polyetheretherketone (PEEK) is a chemically inert polymer that is insoluble in conventional solvents. PEEK's great potential in tissue engineering applications arises from its ability to not induce adverse reactions when in contact with biological tissues and its mechanical properties, which are similar to those of human bone. These exceptional features are limited by the bio-inertness of PEEK, which causes poor osteogenesis on the implant surface. Here, we demonstrated that the covalent grafting of the sequence (48-69) mapped on the BMP-2 growth factor (GBMP1α) significantly enhances the mineralization and gene expression of human osteoblasts. Different chemical methods were employed for covalently grafting the peptide onto 3D-printed PEEK disks: (a) the reaction between PEEK carbonyls and amino-oxy groups inserted in the peptides' N-terminal sites (oxime chemistry) and (b) the photoactivation of azido groups present in the peptides' N-terminal sites, which produces nitrene radicals able to react with PEEK surface. The peptide-induced PEEK surface modification was assessed using X-ray photoelectron measurements, while the superficial properties of the functionalized material were analyzed by means of atomic force microscopy and force spectroscopy. Live and dead assays and SEM measurements showed greater cell cover on functionalized samples than the control, without any cytotoxicity induction. Moreover, functionalization improved the rate of cell proliferation and the amount of calcium deposits, as demonstrated by the AlamarBlue™ and alizarin red results, respectively. The effects of GBMP1α on h-osteoblast gene expression were assayed using quantitative real-time polymerase chain reaction.