Hybrid pH-Responsive Au@p4VP Microgels as Platform for Selective SERS Analysis

We present the synthesis a of pH-responsive core@shell hybrid microgel. This colloidal system is formed by a 55 nm Au core individually covered by a polymeric pH-sensitive shell of poly(4-vinylpyridine), that we denote as Au@p4VP. Initially, we control the microgel thickness from 51 to 10 nm, and we confirm the pH- responsive capability of Au@p4VP by DLS measurements, showing a swelling degree, which depends on the pH of the media and the crosslinker density within the polymer network. We also prove the hybrid structure by plotting the UV-vis spectra at different pH values, showing a surface plasmon band displacement in function of pH. Thus, at acidic pH the microgel swells due to the electrostatic repulsion created into the polymer matrix, while at high pH, the microgel structure collapses because of the reduction in the electrostatic repulsion and the increment of the hydrophobic interactions. This capability is exploited to introduce doxorubicin molecules into the microgel network which are detected by surface- enhanced Raman spectroscopy (SERS). After increasing the pH of the solution, the captured molecules are brought in close proximity to the surface of the metallic core, enhancing its detection by SERS.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Tripod-shaped penta (p-phenylene)s for the functionalization of silicon surfaces

In order to obtain nanostructured thin films to be used in biosensor devices, several chemical functionalization methods have been developed, such as Click chemistry or Suzuki carbon-carbon coupling reactions on surfaces.1 With the aim to control the orientation and spacing between grafted functional groups on a surface, tripodal oligo (p-phenylene)s have become the ideal anisotropic adsorbates due to their shape-persistent and self-standing characteristics.2 Here we report the synthesis and characterization of several tripod-shaped oligo(p-phenylene)s molecules with legs composed of five phenylene units, compounds 1, 2 and 3. In these structures, each leg is end-capped with an NH-Boc, NH2 and N3 group, respectively. The functional arm contains an acetylene group. The presented synthesis has as key step the Pd-catalyzed Suzuki cross-coupling reaction. In particular, a iodine derivative from the silicon core molecule reacts with the appropriate tetra(p-phenylene) boron derivative, thus generating the final tripod-shaped structure. The azide end-capped leg in 3 is specifically designed for its covalent incorporation on alkynyl terminated silicon surfaces by an easy and reproducible way. As a preliminary study, we present the alkynyl-functionalized silicon wafers nanostructuration with tripod 3 through the cooper catalyzed alkyne-azide cycloaddition (CuAAC) click reaction.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Thermorresponsive magnetic nanoparticles as target drug delivery for cancer treatment

In this research, temperature sensitive microgels with magnetic core for controlled release of 5-fluoruracil was synthesized. Magnetic nanoparticles (Fe3O4) were prepared by coprecipitation method and the surface was functionalized by acrylic acid. Polymer poly(N-isopropylacrylamide) (PNIPAM) were grown by free radical polymerization in presence of cross-liker and initiator. The size of the polymer was manipulated by changing the mole percent of the crosslinker and evaluated for their morphology (TEM), particle size, zeta potential, loading efficiency, drug content and drug release. Furthermore, microgels were tagged with FITC, a fluorochrome which could be applied for cell imaging. Cytotoxicity studies revealed that the microgels were not toxic. These complex nanoparticles (Fe3O4/pNIPAM/FITC/5-Fu) appear to be a great promise to be used in controlled drug delivery and tumor targeting.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Comparative study of dopaminergic activity of tetrahydro-1H-[3]-benzazepines and their precursors

The discovery of the tetrahydro-1H-[3]-benzazepine SCH23390 [1], represented one of the most important advances in the study of dopaminergic receptors due to their behavior as a selective D1 receptor antagonist. The high affinity and selectivity of this tetrahydro-1H-[3]-benzazepine has led to the search for new structures because of their potential dopaminergic activity, especially 1-aryl-substituted tetrahydro-1H-[3]-benzazepines. Furthermore, their precursors, the tetrahydroisoquinolines 1-substituted have shown to have activity for D1 and D2 dopaminergic receptors.[2] We have carried out the synthesis of tetrahydro-1H-[3]-benzazepines 1,2-di-substituted by Stevens rearrangement (SR) on tetrahydroisoquinolinium salts. Stevens rearrangement is an efficient regio- and diastereoselective synthetic methodology. [3a,b] As part of our studies, we have performed the synthesis of benzazepines with modifications at the C-1 and C-2 positions with chlorine and hydroxyl groups at A-ring which is an important factor to modulate affinity at dopaminergic receptors. The interaction of these molecules with D1 and D2 dopaminergic receptors have been studied to establish a structure-activity relationship by radioligand binding assays.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Study and characterization of modified silicon surfaces with organic molecules

Nanostructured thin films and subsequent biofunctionalization of silicon substrates are essential for the development of biosensors devices. The formation of organic monolayers on silicon substrates via Si-C bound allows specific interactions with biomolecules and presents several advantages like greater detection sensitivity and stability against hydrolytic cleavage.1 In this sense, to control the orientation and spacing between grafted functional moieties on the surface, tripodal oligo (p-phenylene)s have become ideal anisotropic adsorbates due to their shape-persistent and selfstanding characteristics.2 On the other hand, biomolecules such as tehtahydro[3]benzazepines are well-known to contain in their structure a phenetylamine skeleton, which is also present in dopaminergic receptors and drugs, therefore these molecules have a remarkable interest in medicinal chemistry. Here we report the synthesis and characterization of several tetrahydro[3]benzazepines and tripod-shaped oligo(p-phenylene)s which were suitably functionalized for its subsequent adsorption on silicon surfaces by hydrosilylation and/or CuAAc click reaction. X-ray photoemission spectroscopy (XPS) and atomic force microscopy (AFM) analysis were also carried out to reveal the presence of the grafted molecules on the different Si surfaces.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Synthesis of New Analogues of the Bengamides to encapsulate in magnetic nanoparticles

The development and identification of new antitumoral has become a research area of great interest and maximum priority due to secondary effects of current antitumoral and the appearance of tumours resistant to these agents. Marine sponges corresponding to the Jaspidae family have proved to be a prolific source of bioactive natural products. Among these, the Bengamides have showed an important biological profile, including antitumor, antibiotic and anthelmintic properties. Due to the interest of theses natural products, we describe a study directed towards the total synthesis of this class of compounds. Then we encapsulate Bengamides in temperature sensitive microgels with a magnetic core. Magnetic nanoparticles (Fe3O 4) were prepared by coprecipitation method and the surface was functionalized by acrylic acid. Polymer poly(N-isopropylacrylamide) (PNIPAM) were grown by free radical polymerization in presence of cross-liker and initiator.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Comparative Study of p-Aminothiophenol Adsorption by Surface-Enhanced Raman Spectroscopy

The organic compound p-aminothiophenol (PATP, HS-Ph-NH2) has become very popular for checking the enhancement capability of novel substrates due to its very intense SERS spectra. SERS of PATP on metal nanoparticles is significantly different from its ordinary Raman spectra and it is very dependent on the particular experimental conditions. It has been demonstrated that PATP molecule can chemically transform to 4,4′-dimercaptoazobenzene (DMAB) upon adsorption, being this new compound the responsible of giving rise to new SERS bands [1]. In this work, we have studied the adsorption behavior of PATP on different metal substrates: silver electrode [2], silver colloids and bimetallic nanoparticles made of gold and silver. Additionally, theoretical DFT calculations have been performed for supporting the experimental data. The analysis of the SERS results of the PAPT adsorbed on this type of nanoparticles leads us to deduce a very different catalytic capability in the dimerization of this adsorbate that depends directly on the morphology of the nanoparticle. These preliminary but fascinating results on these bimetallic systems are going to be the focus of further experiment in order to quantify the catalytic capabilities of these interesting nanoparticles. REFERENCES 1. Y.F. Huang, H.P. Zhu, G.K. Liu, D.Y. Wu, B. Ren, Z.Q. Tian, When the signal is not from the original molecule to be detected: Chemical transformation of para-Aminothiophenol on ag during the SERS measurement, J. Am. Chem. Soc. 132 (2010) 9244–9246. 2. M.R. Lopez-Ramirez, D. Aranda Ruiz, F.J. Avila Ferrer, S.P. Centeno, J.F. Arenas, J.C. Otero, J. Soto, Analysis of the Potential Dependent Surface-Enhanced Raman Scattering of p-Aminothiophenol on the Basis of MS-CASPT2 Calculations, J. Phys. Chem. C. 120 (2016) 19322–19328.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Electrospun Nanofibers: Recent Applications in Drug Delivery and Cancer Therapy

Polymeric nanofibers (NFs) have been extensively reported as a biocompatible scaffold to be specifically applied in several researching fields, including biomedical applications. The principal researching lines cover the encapsulation of antitumor drugs for controlled drug delivery applications, scaffolds structures for tissue engineering and regenerative medicine, as well as magnetic or plasmonic hyperthermia to be applied in the reduction of cancer tumors. This makes NFs useful as therapeutic implantable patches or mats to be implemented in numerous biomedical researching fields. In this context, several biocompatible polymers with excellent biocompatibility and biodegradability including poly lactic-co-glycolic acid (PLGA), poly butylcyanoacrylate (PBCA), poly ethylenglycol (PEG), poly (epsilon-caprolactone) (PCL) or poly lactic acid (PLA) have been widely used for the synthesis of NFs using the electrospun technique. Indeed, other types of polymers with stimuli-responsive capabilities has have recently reported for the fabrication of polymeric NFs scaffolds with relevant biomedical applications. Importantly, colloidal nanoparticles used as nanocarriers and non-biodegradable structures have been also incorporated by electrospinning into polymeric NFs for drug delivery applications and cancer treatments. In this review, we focus on the incorporation of drugs into polymeric NFs for drug delivery and cancer treatment applications. However, the principal novelty compared with previously reported publications is that we also focus on recent investigations concerning new strategies that increase drug delivery and cancer treatments efficiencies, such as the incorporation of colloidal nanoparticles into polymeric NFs, the possibility to fabricate NFs with the capability to respond to external environments, and finally, the synthesis of hybrid polymeric NFs containing carbon nanotubes, magnetic and gold nanoparticles, with magnetic and plasmonic hyperthermia applicability.This research was funded by the Comunidad de Madrid, Spain fellowship “Atracción de Talento Investigador” (2018-T1/IND-10736), Consejería de Salud de la Junta de Andalucía (project PI-0476-2016 and PI-0102-2017) and CICYT, Spain (project CTQ16-76311)

Au@p4VP core@shell pH-sensitive nanocomposites suitable for drug entrapment

11 p.-2 schem.-1 graph. abst.We synthesize and characterize pH-responsive hybrid nanocomposites with SERS and drug loading applications. This colloidal system is structured by spherical 50 nm Au cores individually coated by a pH-sensitive shell of poly4-vinylpyridine (Au@p4VP). The synthesis of these hybrid nanocomposites is performed in two steps, a first one involves the fabrication of vinyl-functionalized Au nanoparticles, and a second one includes the controlled overgrowth of a p4VP shell by free radical polymerization. As a result, Au@p4VP hybrid systems with a mean diameter ranging from 150 to 57 nm are obtained upon varying the monomer concentration at synthesis. Au@p4VP nanocomposite exhibits pH-response capabilities, confirmed by cryo-TEM analysis, Small Angle X-ray Scattering (SAXS) and Zeta Potential (ZP) measurements at different pH conditions. The Au@p4VP particles also display a controllable swelling response, which depends on the cross-linker density within the polymer. This swelling capability is analyzed by Dynamic Light Scattering (DLS), and UV–vis spectroscopy at different pHs. The pH-responsive capability is here exploited for the chemical entrapment of doxorubicin hydrochloride (Dox) into the polymer network. The presence of this molecule is resolved by Surface Enhanced Raman Spectroscopy (SERS) measurements. The entrapment efficiency of Dox by the Au@p4VP system is determined via NMR spectroscopy of the supernatants.JCR acknowledges funding from UOC, internal grant N116139473, aimed at enhancing submission to H2020 calls. RCC, JLR and JRR acknowledge financial support from the Spanish MINECO projects CTQ2013-48418P, CTQ2016-76311-R, BFU2016-75319-R and MAT2014-55065R. IF, RCC and ABRM thank the financial support given by Junta de Andalucía (Spain) under the project number P12-FQM-2668. J.F.D acknowledges the networking contributions by the COST actions CM1407 and CM1470.Peer reviewe