Design of anisotropic nanostructures for light control

El rápido avance en métodos de micro- y nanofabricación, tanto teórica como experimentalmente, han hecho posible a día de hoy que podamos controlar el flujo de luz con una precisión sin precedentes. Los metamateriales y las metasuperficies son nanoestructuras compuestas a partir de celdas unidad dise˜nadas, de forma que permitan manipular la luz con una respuesta estipulada. Como resultado de esto, los metamateriales han proporcinoado un gran número de posibles aplicaciones nuevas que antes eran inconcebibles. En esta Tesis Doctoral nos hemos centrado en el uso de estos metamateriales excepcionales para conseguir, específicamente, partículas indetectables y también para controlar el modelado de haces de luz. El objetivo principal de esta Tesis es proponer nuevas estructuras fotónicas basadas en metamateriales multicapa metal-dieléctricos que, gracias a su alta anisotropía de forma, son capaces de generar distribuciones de luz altamente localizadas, así como respuestas ópticamente inertes en el campo lejano. Hemos analizado el mecanismo para conseguir la cancelación de la dispersión en nanopartículas con simetría cilíndrica. Es posible ajustar con gran precisión la cancelación de la dispersión a diferentes longitudes de onda para conseguir invisibilidad si tenemos un control preciso tanto de la morfología como de la combinación apropiada de los materiales. Por otro lado, teniendo un dise˜no adecuado de metarrecubrimientos de tama˜no alrededor del nanómetro, podemos conseguir una fuerte focalización de ondas electromagnéticas con gran apertura numérica. Además, dado un campo convergente estos metarrecubrimientos pueden aumentar de forma significativa la apertura numérica. Es más, usando las metasuperficies dise˜nadas se puede moldear el haz para transformar ondas convergentes de gran angular en haces acelerados que presevan su forma. El trabajo que hemos llevado a cabo no se limita exclusivamente a desarrollos basados en fundamentos teóricos y simulaciones numéricas, sino que también nos involucramos en tareas experimentales. Siguiendo esta dirección, estudiamos las ondas de superficie de Dyakonov (DSWs), que se pueden encontrar en la interfase entre un medio birrefringente y otro isótropo. La excitación ocurre en el campo cercano bajo fotoluminiscencia, y la prueba de la existencia de las DSWs se basa en la determinación experimental de su constante de propagación compleja, cuya parte imaginaria es significativamente menor que la encontrada tanto en modos guiados como en leaky modes.The rapid theoretical and experimental advances in micro- and nanofabrication methods has currently made possible the governing of light flow with unprecedented control. Metamaterials and metasurfaces are engineered nanostructures composed by designed building blocks with the ability to manipulate light under a prescribed response. As a result, metamaterials provide a high number of novel potential applications which were previously inconceivable. This Ph.D. Thesis explores on some uses of these exceptional metamaterials, specifically to achieve optical undetectability and controlled beamshaping. The main objective of this Thesis is the proposal of new photonic structures based on metal-dielectric multilayered metamaterials, which due to their high form anisotropy are capable of generating highly localized light distributions, as well as optically inert responses in the far field. The mechanism of scattering cancellation is thoroughly analyzed in nanoparticles of cylindrical symmetry. With an accurate control of a multilayered morphology and a proper combination of materials, it is possible to fine-tune the scattering cancellation at different wavelengths to achieve invisibility. Secondly, an adequate design of a nonplanar metacoating in the nanoscale gives us the ability of achieving tight focusing of high numerical-aperture electromagnetic waves. Moreover, the use of the engineered metasurfaces may execute a beam shaping to transform wide-angle converging waves into shape-preserving accelerating beams. The work developed here is not limited exclusively to developments based on theoretical foundations and numerical simulations, but also an attempt to immerse into the experimental labor. In this direction we studied the Dyakonov surface waves (DSWs), which can be found at the interface between a birefringent medium and another isotropic medium. The excitation occurs in the near field under photoluminescence, and the evidence of the existence of the DSWs is based on the experimental determination of its complex propagation constant, whose imaginary part is significantly smaller compared to that found in the guided and leaky modes in the surrounding media

Ultrathin high-index metasurfaces for shaping focused beams

The volume size of a converging wave, which plays a relevant role in image resolution, is governed by the wavelength of the radiation and the numerical aperture (NA) of the wavefront. We designed an ultrathin (λ/8 width) curved metasurface that is able to transform a focused field into a high-NA optical architecture, thus boosting the transverse and (mainly) on-axis resolution. The elements of the metasurface are metal-insulator subwavelength gratings exhibiting extreme anisotropy with ultrahigh index of refraction for TM polarization. Our results can be applied to nanolithography and optical microscopy.Spanish Ministry of Economy and Competitiveness (MEC) (TEC2013-50416-EXP)

Evaluation of Poly(N-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells

MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells' function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(N-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together.This research was supported by the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain) and Co-financed by the European Union (FEDER) “A way to make Europe” (project references SBPLY/17/000376 and SBPLY/21/180501/000097) and by the Ministerio de Ciencia, Innovación y Universidades (RTI2018-096328-B-I00). Altea Soto was funded by the Council of Education, Culture and Sports of the Regional Government of Castilla La Mancha (Spain) M. Asunción Barreda-Manso is funded by the Council of Health of the Regional Government of Castilla La Mancha (Spain), through: “Convocatoria de Ayudas Regionales a la Investigación en Biomedicina y Ciencias de la Salud” (II-2020_05). Irene Novillo Algaba is funded by the Next Generation Funds of the European Union through the “Programa Investigo”.Peer reviewe

Rational engineering of a human GFP-like protein scaffold for humanized targeted nanomedicines

Green fluorescent protein (GFP) is a widely used scaffold for protein-based targeted nanomedicines because of its high biocompatibility, biological neutrality and outstanding structural stability. However, being immunogenicity a major concern in the development of drug carriers, the use of exogenous proteins such as GFP in clinics might be inadequate. Here we report a human nidogen-derived protein (HSNBT), rationally designed to mimic the structural and functional properties of GFP as a scaffold for nanomedicine. For that, a GFP-like β-barrel, containing the G2 domain of the human nidogen, has been rationally engineered to obtain a biologically neutral protein that self-assembles as 10nm-nanoparticles. This scaffold is the basis of a humanized nanoconjugate, where GFP, from the well-characterized protein T22-GFP-H6, has been substituted by the nidogen-derived GFP-like HSNBT protein. The resulting construct T22-HSNBT-H6, is a humanized CXCR4-targeted nanoparticle that selectively delivers conjugated genotoxic Floxuridine into cancer CXCR4+ cells. Indeed, the administration of T22-HSNBT-H6-FdU in a CXCR4-overexpressing colorectal cancer mouse model results in an even more efficient selective antitumoral effect than that shown by its GFP-counterpart, in absence of systemic toxicity. Therefore, the newly developed GFP-like protein scaffold appears as an ideal candidate for the development of humanized protein nanomaterials and successfully supports the tumor-targeted nanoscale drug T22-HSNBT-H6-FdU.Patricia Álamo and Juan Cedano contributed equally to this work. The authors are indebted to Agencia Estatal de Investigación (AEI) and to Fondo Europeo de Desarrollo Regional (FEDER) (grant BIO2016-76063-R, AEI/FEDER, UE), to AGAUR (2017SGR-229) and CIBER-BBN (project NANOPROTHER), granted to AV, to CIBER-BBN (project NANOSCAPE and NANOLINK) and ISCIII (PI20/00400 co-funding FEDER) granted to UU, to ISCIII (PI15/00272 co-founding FEDER) granted to EV and to ISCIII (PIE15/00028 and PI18/00650, co-funding FEDER) and AGAUR (2017 SGR 865 GRC) granted to RM. We are also indebted to CERCA programme (Generalitat de Catalunya) and to the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) that is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III, with assistance from the European Regional Development Fund. We also appreciate the support from the COST-Action Nano2Clinics. Protein production has been partially performed by the ICTS “NANBIOSIS”, more specifically by the Protein Production Platform of CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN)/ IBB, at the UAB sePBioEs scientific-technical service (http://www.nanbiosis.es/portfolio/u1-protein-production-platform-ppp/), and the nanoparticle size analysis by the Biomaterial Processing and Nanostructuring Unit. Synthesis of thiolated oligo-FdU was performed by the ICTS NANBIOSIS Oligonucleotide Synthesis Platform (CIBER-BBN). The in vivo work was performed by the ICTS NANBIOSIS of the CIBER-BBN Nanotoxicology Unit (http://www.nanbiosis.es/portfolio/u18-nanotoxicology-unit/). We are indebted to Servei de Microscopia from UAB for their excellent confocal and electronic microscopy services. We are also indebted to Servei de Cultius Celulars i Anticossos (SCAC) form UAB for their excellent cell culture and flow cytometry facilities and especially to Fran Cortes for his excellent technical support. We are thankful to Dra. Marta Taulés from CCiT-UB for her help in SPR experiments and analysis. We are also thankful to Luis Carlos Navas from Institut d'Investigacions biomèdiques Sant Pau (IIB Sant Pau) for his technical support in immunohistochemistry experiments. UU and LMCD were supported by Miguel Servet (CP19/00028) and PFIS (FI19/00148) contracts respectively from ISCIII co-funded by European Social Fund (ESF investing in your future). NS was supported by a pre-doctoral fellowship from the Government of Navarra and LAC was supported by AECC Scientific Foundation grant postdoctoral fellow. AV received an ICREA ACADEMIA award.Peer reviewe

Experimental Measurement of Carbohydrate–Aromatic Stacking in Water by Using a Dangling-Ended DNA Model System

8 páginas, 3 figuras, 2 tablas, 2 esquemasProtein–carbohydrate recognition is of fundamental importance for a large number of biological processes; carbohydrate–aromatic stacking is a widespread, but poorly understood, structural motif in this recognition. We describe, for the first time, the measurement of carbohydrate–aromatic interactions from their contribution to the stability of a dangling-ended DNA model system. We observe clear differences in the energetics of the interactions of several monosaccharides with a benzene moiety depending on the number of hydroxy groups, the stereochemistry, and the presence of a methyl group in the pyranose ring. A fucose–benzene pair is the most stabilizing of the studied series (−0.4 Kcal mol−1) and this interaction can be placed in the same range as other more studied interactions with aromatic residues of proteins, such as Phe–Phe, Phe–Met, or Phe–His. The noncovalent forces involved seem to be dispersion forces and nonconventional hydrogen bonds, whereas hydrophobic effects do not seem to drive the interaction.We thank the Ministry of Science and Education for funding (grant no.: CTQ-2006-01123/BQU) and for a Ramón y Cajal contract (J.C.M.).Peer reviewe

Accelerating wide-angle converging waves in the near field

We show that a wide-angle converging wave may be transformed into a shape-preserving accelerating beam having a beam-width near the diffraction limit. For that purpose, we followed a strategy that is particularly conceived for the acceleration of nonparaxial laser beams, in contrast to the well-known method by Siviloglou et al (2007 Phys. Rev. Lett. 99 213901). The concept of optical near-field shaping is applied to the design of non-flat ultra-narrow diffractive optical elements. The engineered curvilinear caustic can be set up by the beam emerging from a dynamic assembly of elementary gratings, the latter enabling to modify the effective refractive index of the metamaterial as it is arranged in controlled orientations. This light shaping process, besides being of theoretical interest, is expected to open up a wide range of broadband application possibilities.This research was funded by the Spanish Ministry of Economy and Competitiveness under the project TEC2011-29120-C05-01. M Naserpour, acknowledges financial support from the Ministry of Science, Research and Technology of Iran