Synthesis of silver nanoparticles using DL-alanine for ESR dosimetry applications

The potential use of alanine for the production of nanoparticles is presented here for the first time. Silver nanoparticles were synthesized using a simple green method, namely the thermal treatment of silver nitrate aqueous solutions with in-alanine. The latter compound was employed both as a reducing and a capping agent. Particles with average size equal to 7.5 nm, face-centered cubic crystalline structure, narrow size distribution, and spherical shape were obtained. Interaction between the silver ions present on the surface of the nanoparticles and the amine group of the DL-alanine molecule seems to be responsible for reduction of the silver ions and for the stability of the colloid. The bio-hybrid nanocomposite was used as an ESR dosimeter. The amount of silver nanoparticles in the nanocomposite was not sufficient to cause considerable loss of tissue equivalency. Moreover, the samples containing nanoparticles presented increased sensitivity and reduced energetic dependence as compared with pure DL-alanine, contributing to the construction of small-sized dosimeters. (C) 2011 Elsevier Ltd. All rights reserved.

Post-receptor IGF1 insensitivity restricted to the MAPK pathway in a Silver-Russell syndrome patient with hypomethylation at the imprinting control region on chromosome 11

Background: Hypomethylation of the paternal imprinting center region 1 (ICR1) is the most frequent molecular cause of Silver-Russell syndrome (SRS). Clinical evidence suggests that patients with this epimutation have mild IGF1 insensitivity. Objective: To assess in vitro IGF1 action in fibroblast culture from a patient with SRS and IGF1 insensitivity. Methods: Fibroblast cultures from one patient with SRS due to ICR1 demethylation and controls were established. The SRS patient has severe growth failure, elevated IGF1 level, and poor growth rate during human recombinant GH treatment. IGF1 action was assessed by cell proliferation, AKT, and p42/44-MAPK phosphorylation. Gene expression was determined by real-time PCR. Results: Despite normal IGF1R sequence and expression, fibroblast proliferation induced by IGF1 was 50% lower in SRS fibroblasts in comparison with controls. IGF1 and insulin promoted a p42/44-MAPK activation in SRS fibroblasts 40 and 36%, respectively, lower than that in control fibroblasts. On the other hand, p42/44-MAPK activation induced by EGF stimulation was only slightly reduced (75% in SRS fibroblasts in comparison with control), suggesting a general impairment in MAPK pathway with a greater impairment of the stimulation induced by insulin and IGF1 than by EGF. A PCR array analysis disclosed a defect in MAPK pathway characterized by an increase in DUSP4 and MEF2C gene expressions in patient fibroblasts. Conclusion: A post-receptor IGF1 insensitivity was characterized in one patient with SRS and ICR1 hypomethylation. Although based on one unique severely affected patient, these results raise an intriguing mechanism to explain the postnatal growth impairment observed in SRS patients that needs confirmation in larger cohorts.

Functionalization of gold and silver nanoparticles with diphenyl dichalcogenides probed by surface enhanced Raman scattering

This paper describes a surface-enhanced Raman scattering (SERS) systematic investigation regarding the functionalization of gold (Au) and silver (Ag) nanoparticles with diphenyl dichalcogenides, i.e. diphenyl disulfide, diphenyl diselenide, and diphenyl ditelluride. Our results showed that, in all cases, functionalization took place with the cleavage of the chalcogenchalcogen bond on the surface of the metal. According to our density functional theory calculations, the molecules assumed a tilted orientation with respect to the metal surface for both Au and Ag, in which the angle of the phenyl ring relative to the metallic surface decreased as the mass of the chalcogen atom increased. The detected differences in the ordinary Raman and SERS spectra were assigned to the distinct stretching frequencies of the carbonchalcogen bond and its relative contribution to the ring vibrational modes. In addition, the SERS spectra showed that there was no significant interaction between the phenyl ring and the surface, in agreement with the tilted orientation observed from our density functional theory calculations. The results described herein indicate that diphenyl dichalcogenides can be successfully employed as starting materials for the functionalization of Au nanoparticles with organosulfur, organoselenium, and organotellurium compounds. On the other hand, diphenyl disulfide and diphenyl diselenide could be employed for the functionalization of Ag nanoparticles, while the partial oxidation of the organotellurium unit could be detected on the Ag surface. Copyright (C) 2011 John Wiley & Sons, Ltd.

Silver-gold nanotubes containing hot spots on their surface: facile synthesis and surface-enhanced Raman scattering investigations

We report the synthesis of silver-gold nanotubes containing hot spots along their surface. The Ag-Au nanotubes exhibited exceptional SERS properties compared to silver nanowires, enabling the detection of crystal violet in the 10(-10) M regime, as well as 9-nitroanthracene and benzo[a] pyrene at 3.3 x 10(-7) M.

Application of Polysaccharide Hydrogels in Adsorption and Controlled-Extended Release of Fertilizers Processes

This article studied the applicability of poly(acrylamide) and methylcellulose (PAAm-MC) hydrogels as potential delivery vehicle for the controlled-extended release of ammonium sulfate (NH(4))(2)SO(4) and potassium phosphate (KH(2)PO(4)) fertilizers. PAAm-MC hydrogels with different acrylamide (AAm) and MC concentrations were prepared by a free radical polymerization method. The adsorption and desorption kinetics of fertilizers were determined using conductivity measurements based on previously built analytical curve. The addition of MC in the PAAm chains increased the quantities of (NH(4))(2)SO(4) and KH(2)PO(4) loaded and extended the time and quantities of fertilizers released. Coherently, both loading and releasing processes were strongly influenced by hydrophilic properties of hydrogels (AAm/MC mass proportion). The best sorption (124.0 mg KH(2)PO(4)/g hydrogel and 58.0 mg (NH(4))(2)SO(4)/g hydrogel) and desorption (54.9 mg KH(2)PO(4)/g hydrogel and 49.5 mg (NH(4))(2)SO(4)/g hydrogel) properties were observed for 6.0% AAm-1.0% MC hydrogels (AAm/MC mass proportion equal 6), indicating that these hydrogels are potentially viable to be used in controlled-extended release of fertilizers systems. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci 123: 2291-2298, 2012

Development of cellulose-based bactericidal nanocomposites containing silver nanoparticles and their use as active food packaging

The use of nanomaterials, including metallic as active fillers in polymeric nanocomposites for food packaging has been extensively investigated. Silver nanoparticles (AgNPs), in particular, have been exploited for technological applications as bactericidal agents. In this paper, AgNPs were incorporated into a hydroxypropyl methylcellulose (HPMC) matrix for applications as food packaging materials. The average sizes of the silver nanoparticles were 41 nm and 100 nm, respectively. Mechanical analyses and water vapor barrier properties of the HPMC/AgNPs nanocomposites were analysed. The best results were observed for films containing smaller (41 nm) AgNPs. The antibacterial properties of HPMC/AgNPs thin films were evaluated based on the diameter of inhibition zone in a disk diffusion test against Escherichia coli (E. coil) and Staphylococcus aureus (S. aureus). The disk diffusion studies revealed a greater bactericidal effectiveness for nanocomposites films containing 41 nm Ag nanoparticles. (C) 2011 Elsevier Ltd. All rights reserved.

Antimicrobial effectiveness of silver nanoparticles co-stabilized by the bioactive copolymer pluronic F68

Abstract Background Silver nanoparticles (AgNps) have attracted much interest in biomedical engineering, since they have excellent antimicrobial properties. Therefore, AgNps have often been considered for incorporation into medical products for skin pathologies to reduce the risk of contamination. This study aims at evaluating the antimicrobial effectiveness of AgNps stabilized by pluronic™ F68 associated with other polymers such as polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Methods AgNps antimicrobial activity was evaluated using the minimum inhibitory concentration (MIC) method. The action spectrum was evaluated for different polymers associated with pluronic™ F68 against the gram negative bacteria P. aeuroginosa and E. coli and the gram positive bacteria S. Aureus. Results AgNps stabilized with PVP or PVA and co-stabilized with pluronic™ F68 are effective against E. coli and P. aeruginosa microorganisms, with MIC values as low as 0.78% of the concentration of the original AgNps dispersion. The antimicrobial action against S. aureus is poor, with MIC values not lower than 25%. Conclusions AgNps stabilized by different polymeric systems have shown improved antimicrobial activity against gram-negative microorganisms in comparison to unstabilized AgNps. Co-stabilization with the bioactive copolymer pluronic™ F68 has further enhanced the antimicrobial effectiveness against both microorganisms. A poor effectiveness has been found against the gram-positive S. aureus microorganism. Future assays are being delineated targeting possible therapeutic applications.

Processamento auditivo, leitura e escrita na síndrome de Silver-Russell: relato de caso

O objetivo deste trabalho foi descrever os aspectos fonoaudiológicos de processamento auditivo, leitura e escrita de um paciente do gênero masculino com diagnóstico de síndrome de Silver-Russell. Aos dois meses de idade o paciente apresentava déficit pôndero-estatural; frontal amplo; orelhas pequenas, proeminentes e com baixa implantação; palato ogival; discreta micrognatia; esclera azulada; manchas café-com-leite; sobreposição do primeiro e segundo artelhos à direita; refluxo gastroesofágico; voz e choro agudos; atraso leve no desenvolvimento neuropsicomotor; e dificuldade de ganhar peso, recebendo o diagnóstico da síndrome. Na avaliação psicológica, realizada aos 8 anos de idade, o paciente apresentou nível intelectual normal, com dificuldades cognitivas envolvendo atenção sustentada, concentração, memória verbal imediata e processos emocionais e comportamentais. Para avaliação da leitura e escrita e de seus processos subjacentes, realizada aos 9 anos de idade foram utilizados os testes de Compreensão Leitora de Textos Expositivos, Perfil das Habilidades Fonológicas, Teste de Discriminação Auditiva, escrita espontânea, Teste de Desempenho Escolar (TDE), teste de Nomeação Automática Rápida e prova de memória de trabalho fonológica. Apresentou dificuldades em todos os testes, estando as pontuações abaixo do esperado para sua idade. Na avaliação do processamento auditivo foram realizados testes monóticos, dióticos e dicóticos. Foram encontradas alterações nas habilidades de atenção auditiva sustentada e seletiva, memória sequencial para sons verbais e não-verbais, e resolução temporal. Conclui-se que o paciente apresenta alterações na aprendizagem da leitura e escrita que podem ser secundários a síndrome de Silver-Russell, porém tais dificuldades também podem ser decorrentes das alterações em habilidades do processamento auditivo.

N-Heterocyclic carbene complexes of silver, rhodium and iron: structures, dynamics and catalysis

The research performed in the framework of this Master Thesis has been directly inspired by the recent work of an organometallic research group led by Professor Maria Cristina Cassani on a topic related to the structures, dynamics and catalytic activity of N-heterocyclic carbene-amide rhodium(I) complexes1. A series of [BocNHCH2CH2ImR]X (R = Me, X = I, 1a’; R = Bz, X = Br, 1b’; R = trityl, X = Cl, 1c’) amide-functionalized imidazolium salts bearing increasingly bulky N-alkyl substituents were synthetized and characterized. Subsequently, these organic precursors were employed in the synthesis of silver(I) complexes as intermediate compounds on a way to rhodium(I) complexes [Rh(NBD)X(NHC)] (NHC = 1-(2-NHBoc-ethyl)-3-R-imidazolin-2-ylidene; X = Cl, R = Me (3a’), R = Bz (3b’), R = trityl (3c’); X = I, R = Me (4a’)). VT NMR studies of these complexes revealed a restricted rotation barriers about the metal-carbene bond. However, while the rotation barriers calculated for the complexes in which R = Me, Bz (3a’,b’ and 4a) matched the experimental values, this was not true in the trityl case 3c’, where the experimental value was very similar to that obtained for compound 3b’ and much smaller with respect to the calculated one. In addition, the energy barrier derived for 3c’ from line shape simulation showed a strong dependence on the temperature, while the barriers measured for 3a’,b’ did not show this effect. In view of these results and in order to establish the reasons for the previously found inconsistency between calculated and experimental thermodynamic data, the first objective of this master thesis was the preparation of a series of rhodium(I) complexes [Rh(NBD)X(NHC)] (NHC = 1-benzyl-3-R-imidazolin-2-ylidene; X = Cl, R = Me, Bz, trityl, tBu), containing the benzyl substituent as a chiral probe, followed by full characterization. The second objective of this work was to investigate the catalytic activity of the new rhodium compounds in the hydrosilylation of terminal alkynes for comparison purposes with the reported complexes. Another purpose of this work was to employ the prepared N-heterocyclic ligands in the synthesis of iron(II)-NHC complexes.

Evaluation of Silver European EEL (anguilla anguilla) for the implementation of an Effective EEL Management plan in Mediterranean Coastal Lagoons

This thesis presents SEELF (Sustainable EEL fishery) Index, a methodology for evaluation of European eel (Anguilla anguilla) for the implementation of an effective Eel Management Plan, as defined by EU Regulation No.1100/2007. SEELF uses internal and external indices, age and blood parameters, and selects suitable specimen for restocking; it is also a reliable tool for eel stock management. In fact, SEELF Index, was developed in two versions: SEELF A, to be used in field operations (catch&release, eel status monitoring) and SEELF B to be used for quality control (food production) and research (eel status monitoring). Health status was evaluated also by biomarker analysis (ChE), and data were compared with age of eel. Age determination was performed with otolith reading and fish scale reading and a calibration between the two methods was possible. The study area was the Comacchio lagoon, a brackish coastal lagoon in Italy, well known as an example of suitable environment for eel fishery, where the capability to use the local natural resources has long been a key factor for a successful fishery management. Comacchio lagoon is proposed as an area where an effective EMP can be performed, in agreement with the main features (management of basins, reduction of mortality due to predators,etc.) highlighted for designation of European Restocking Area (ERA). The ERA is a new concept, proposed as a pillar of a new strategy on eel management and conservation. Furthermore, the features of ERAs can be useful in the framework of European Scale Eel Management Plan (ESEMP), proposed as a European scale implementation of EMP, providing a more effectiveness of conservation measures for eel management.

Chitosan based hydrogels for transmucosal drug delivery

The aim of this thesis was the formulation of new chitosan based delivery systems for transmucosal drug administration. Transmucosal routes, such as buccal, vaginal and nasal routes, allow the circumvention of the hepatic first pass metabolism and avoid the gastrointestinal chemical and enzymatic degradations. Moreover, transmucosal drug administration can allow to avoid pain or discomfort caused by injections, when drugs are administered through parenteral routes, thus increasing patient compliance. On the other side, the major disadvantage of transmucosal drug administration is represented by the presence of biological fluids and mucus that can remove drug systems from the application site, thus reducing the contact time between drug and mucosa and consequently, decreasing drug bioavailability. For this reason, in this study, the investigation of chitosan delivery systems as mucoadhesive formulations able to increase drugs residence time and to improve their bioavailability, was taken into account. In the paper 1, buccal films based on chitosan-gelatin complexes were prepared and loaded with propranolol hydrochloride. The complexes were characterized and studied in order to evaluate their physical- chemical properties and their ability to release the drug and to allow its permeation through buccal mucosa. In the paper 2, vaginal inserts based on chitosan/alginate complexes were formulated for local delivery of chlorhexidine digluconate. Tests to evaluate the interaction between the polymers and to study drug release properties were performed, as well as the determination of antimicrobial activity against the patogens responsible of vaginitis and candidosis. In the project 3, chitosan based nanoparticles containing cyclodextrin and other excipients, with the capacity to modify insulin bioavailabity were formulated for insulin nasal delivery. Nanoparticles were characterized in terms of size, stability and drug release. Moreover, in vivo tests were performed in order to study the hypoglycemic reduction in rats blood samples.

Functional dextran-based hydrogels

Dextran-based polymers are versatile hydrophilic materials, which can provide functionalized surfaces in various areas including biological and medical applications. Functional, responsive, dextran based hydrogels are crosslinked, dextran based polymers allowing the modulation of response towards external stimuli. The controlled modulation of hydrogel properties towards specific applications and the detailed characterization of the optical, mechanical, and chemical properties are of strong interest in science and further applications. Especially, the structural characteristics of swollen hydrogel matrices and the characterization of their variations upon environmental changes are challenging. Depending on their properties hydrogels are applied as actuators, biosensors, in drug delivery, tissue engineering, or for medical coatings. However, the field of possible applications still shows potential to be expanded. rnSurface attached hydrogel films with a thickness of several micrometers can serve as waveguiding matrix for leaky optical waveguide modes. On the basis of highly swelling and waveguiding dextran based hydrogel films an optical biosensor concept was developed. The synthesis of a dextran based hydrogel matrix, its functionalization to modulate its response towards external stimuli, and the characterization of the swollen hydrogel films were main interests within this biosensor project. A second focus was the optimization of the hydrogel characteristics for cell growth with the aim of creating scaffolds for bone regeneration. Matrix modification towards successful cell growth experiments with endothelial cells and osteoblasts was achieved.rnA photo crosslinkable, carboxymethylated dextran based hydrogel (PCMD) was synthesized and characterized in terms of swelling behaviour and structural properties. Further functionalization was carried out before and after crosslinking. This functionalization aimed towards external manipulation of the swelling degree and the charge of the hydrogel matrix important for biosensor experiments as well as for cell adhesion. The modulation of functionalized PCMD hydrogel responses to pH, ion concentration, electrochemical switching, or a magnetic force was investigated. rnThe PCMD hydrogel films were optically characterized by combining surface plasmon resonance (SPR) and optical waveguide mode spectroscopy (OWS). This technique allows a detailed analysis of the refractive index profile perpendicular to the substrate surface by applying the Wentzel Kramers Brillouin (WKB) approximation. rnIn order to perform biosensor experiments, analyte capturing units such as proteins or antibodies were covalently coupled to the crosslinked hydrogel backbone by applying active ester chemistry. Consequently, target analytes could be located inside the waveguiding matrix. By using labeled analytes, fluorescence enhancement was achieved by fluorescence excitation with the electromagnetic field in the center of the optical waveguide modes. The fluorescence excited by the evanescent electromagnetic field of the surface plasmon was 2 3 orders of magnitude lower. Furthermore, the signal to noise ratio was improved by the fluorescence excitation with leaky optical waveguide modes.rnThe applicability of the PCMD hydrogel sensor matrix for clinically relevant samples was proofed in a cooperation project for the detection of PSA in serum with long range surface plasmon spectroscopy (LRSP) and fluorescence excitation by LRSP (LR SPFS). rn

Functional hydrogels: ferrogel thin films

Die Kombination magnetischer Nanopartikel (NP) mit temperatursensitiven Polymeren führt zur Bildung neuer Komposit-Materialien mit interessanten Eigenschaften, die auf vielfältige Weise genutzt werden können. Mögliche Anwendungsgebiete liegen in der magnetischen Trennung, der selektiven Freisetzung von Medikamenten, dem Aufbau von Sensoren und Aktuatoren. Als Polymerkomponente können z.B. Hydrogele dienen. Die Geschwindigkeit der Quellgradänderung mittels externer Stimuli kann durch eine Reduzierung des Hydrogelvolumens erhöht werden, da das Quellen ein diffusionskontrollierter Prozess ist. rnIm Rahmen dieser Arbeit wurde ein durch ultraviolettes Licht vernetzbares Hydrogel aus N-isopropylacrylamid, Methacrylsäure und dem Vernetzer 4-Benzoylphenylmethacrylat hergestellt (PNIPAAm-Hydrogel) und mit magnetischen Nanopartikeln aus Magnetit (Fe3O4) kombiniert. Dabei wurde die Temperatur- und die pH-Abhängigkeit des Quellgrades im Hinblick auf die Verwendung als nanomechanische Cantilever Sensoren (NCS) untersucht. Desweiteren erfolgte eine Charakterisierung durch Oberflächenplasmonen- und optischer Wellenleitermoden-Resonanz Spektroskopie (SPR/OWS). Die daraus erhaltenen Werte für den pKa-Wert und die lower critical solution Temperatur (LCST) stimmten mit den bekannten Literaturwerten überein. Es konnte gezeigt werden, dass eine stärkere Vernetzung zu einer geringeren LCST führt. Die Ergebnisse mittels NCS wiesen zudem auf einen skin-effect während des Heizens von höher vernetzten Polymeren hin.rnDie Magnetit Nanopartikel wurden ausgehend von Eisen(II)acetylacetonat über eine Hochtemperaturreaktion synthetisiert. Durch Variation der Reaktionstemperatur konnte die Größe der hergestellten Nanopartikel zwischen 3.5 und 20 nm mit einer Größenverteilung von 0.5-2.5 nm eingestellt werden. Durch geeignete Oberflächenfunktionalisierung konnten diese in Wasser stabilisiert werden. Dazu wurde nach zwei Strategien verfahren: Zum einen wurden die Nanopartikel mittels einer Silika-Schale funktionalisiert und zum anderen Zitronensäure als Tensid eingesetzt. Wasserstabilität ist vor allem für biologische Anwendungen wünschenswert. Die magnetischen Partikel wurden mit Hilfe von Transmissionselektronenmikroskopie (TEM), und superconductive quantum interference device (SQUID) charakterisiert. Dabei wurde eine Größenabhängigkeit der magnetischen Eigenschaften sowie superparamagnetisches Verhalten beobachtet. Außerdem wurde die Wärmeerzeugung der magnetischen Nanopartikel in einem AC Magnetfeld untersucht. rnDie Kombination beider Komponenten in Form eines Ferrogels wurde durch Mischen Benzophenon funktionalisierter magnetischer Nanopartikel mit Polymer erreicht. Durch Aufschleudern (Spin-Coaten) wurden dünne Filme erzeugt und diese im Hinblick auf ihr Verhalten in einem Magnetfeld untersucht. Dabei wurde eine geringes Plastikverhalten beobachtet. Die experimentellen Ergebnisse wurden anschließend mit theoretisch berechneten Erwartungswerten verglichen und mit den unterschiedlichen Werten für dreidimensionale Ferrogele in Zusammenhang gestellt. rn

Functional hydrogels

Hydrogels are used in a variety of applications in daily life, such as super absorbers, contact lenses and in drug delivery. Functional hydrogels that allow the incorporation of additional functionalities have enormous potential for future development. The properties of such hydrogels can be diversified by introducing responsiveness to external stimuli. These crosslinked polymers are known to respond to changes in temperature, pH and pressure, as well as chemical and electrical stimuli, magnetic fields and irradiation. From this responsive behavior possible applications arise in many fields like drug delivery, tissue engineering, purification and implementation as actuators, biosensors or for medical coatings. However, their interaction with biomaterial and way of functioning are yet not fully understood. Therefore, thorough investigations regarding their optical, mechanical and chemical nature have to be conducted. A UV-crosslinkable polymer, consisting of N-isopropylacrylamide, methacrylic acid and the UV-crosslinker 4-benzoylphenyl methacrylate was synthesized. Its composition, determined by a comprehensive NMR study, is equivalent to the composition of the monomer mixture. The chemical characteristics were preserved during the subsequently formation of hydrogel films by photo-crosslinking as proved by XPS. For the optical characterization, e.g. the degree of swelling of very thin films, the spectroscopy of coupled long range surface plasmons is introduced. Thicker films, able to guide light waves were analyzed with combined surface plasmon and optical waveguide mode spectroscopy (SPR/OWS). The evaluation of the data was facilitated by the reverse Wentzel-Kramers-Brillouin (WKB) approximation. The meshsize and proper motion of the surface anchored hydrogels were investigated by fluorescence correlation spectroscopy (FCS), micro photon correlation spectroscopy (µPCS) and SPR/OWS. The studied gels exhibit a meshsize that allowed for the diffusion of small biomolecules inside their network. For future enhancement of probing diffusants, a dye that enables FRET in FCS was immobilized in the gel and the diffusion of gold-nanoparticles embedded in the polymer solution was studied by PCS. These properties can be conveniently tuned by the crosslinking density, which depends on the irradiation dose. Additionally, protocols and components for polymer analogous reactions based on active ester chemistry of the hydrogel were developed. Based on these syntheses and investigations, the hydrogel films are applied in the fields of medical coatings as well as in biosensing as matrix and biomimetic cushion. Their non-adhesive properties were proved in cell experiments, SPR/OWS and ToF-SIMS studies. The functionality and non-fouling property of the prepared hydrogels allowed for adaption to the needs of the respective application.

Synthesis and surface modification of silver and gold nanoparticles. Nanomedicine applications against Glioblastoma Multiforme.

In the last decades noble metal nanoparticles (NPs) arose as one of the most powerful tools for applications in nanomedicine field and cancer treatment. Glioblastoma multiforme (GBM), in particular, is one of the most aggressive malignant brain tumors that nowadays still presents a dramatic scenario concerning median survival. Gold nanorods (GNRs) and silver nanoparticles (AgNPs) could find applications such as diagnostic imaging, hyperthermia and glioblastoma therapy. During these three years, both GNRs and AgNPs were synthesized with the “salt reduction” method and, through a novel double phase transfer process, using specifically designed thiol-based ligands, lipophilic GNRs and AgNPs were obtained and separately entrapped into biocompatible and biodegradable PEG-based polymeric nanoparticles (PNPs) suitable for drug delivery within the body. Moreover, a synergistic effect of AgNPs with the Alisertib drug, were investigated thanks to the simultaneous entrapment of these two moieties into PNPs. In addition, Chlorotoxin (Cltx), a peptide that specifically recognize brain cancer cells, was conjugated onto the external surface of PNPs. The so-obtained novel nanosystems were evaluated for in vitro and in vivo applications against glioblastoma multiforme. In particular, for GNRs-PNPs, their safety, their suitability as optoacoustic contrast agents, their selective laser-induced cells death and finally, a high tumor retention were all demonstrated. Concerning AgNPs-PNPs, promising tumor toxicity and a strong synergistic effect with Alisertib was observed (IC50 10 nM), as well as good in vivo biodistribution, high tumor uptake and significative tumor reduction in tumor bearing mice. Finally, the two nanostructures were linked together, through an organic framework, exploiting the click chemistry azido-alkyne Huisgen cycloaddition, between two ligands previously attached to the NPs surface; this multifunctional complex nanosystem was successfully entrapped into PNPs with nanoparticles’ properties maintenance, obtaining in this way a powerful and promising tool for cancer fight and defeat.