Functionalization of gold nanostars with cationic ß-cyclodextrin-based polymer for drug co-loading and SERS monitoring

Gold nanostars (AuNSs) exhibit modulated plasmon resonance and have a high SERS enhancement factor. However, their low colloidal stability limits their biomedical application as a nanomaterial. Cationic ß-cyclodextrin-based polymer (CCD/P) has low cytotoxicity, can load and transport drugs more efficiently than the corresponding monomeric form, and has an appropriate cationic group to stabilize gold nanoparticles. In this work, we functionalized AuNSs with CCD/P to load phenylethylamine (PhEA) and piperine (PIP) and evaluated SERS-based applications of the products. PhEA and PIP were included in the polymer and used to functionalize AuNSs, forming a new AuNS-CCD/P-PhEA-PIP nanosystem. The system was characterized by UV–VIS, IR, and NMR spectroscopy, TGA, SPR, DLS, zeta potential analysis, FE-SEM, and TEM. Additionally, Raman optical activity, SERS analysis and complementary theoretical studies were used for characterization. Minor adjustments increased the colloidal stability of AuNSs. The loading capacity of the CCD/P with PhEA-PIP was 95 ± 7%. The physicochemical parameters of the AuNS-CCD/P-PhEA-PIP system, such as size and Z potential, are suitable for potential biomedical applications Raman and SERS studies were used to monitor PhEA and PIP loading and their preferential orientation upon interaction with the surface of AuNSs. This unique nanomaterial could be used for simultaneous drug loading and SERS-based detection

Estudio de nanopartículas de Au y de Ag y su interacción con complejos de [beta]ciclodextrina como potenciales sistemas de entrega de fármacos

Doctor en QuímicaLas nanopartículas metálicas (NPsM), específicamente, las nanopartículas de oro (NPsAu) y las nanopartículas de plata (NPsAg), exhiben excelentes propiedades físicas, químicas y biológicas, intrínsecas a su tamaño nanométrico y tienen una aplicación directa en el tratamiento de enfermedades. Se ha logrado diseñar nanosistemas usados para el transporte de fármacos, permitiendo que estos lleguen activos al sitio de acción, atravesando diversas barreras biológicas. Gracias al efecto de plasmón de las NPsM, es posible promover la liberación de un fármaco en células o tejidos específicos de manera controlada a través de terapia fototérmica. Otra manera interesante de modificar las propiedades fisicoquímicas de algún compuesto, es mediante la formación de complejos de inclusión (CI), que se basan en interacciones no convencionales entre una especie llamada matriz con otra denominada huésped. La βciclodextrina (βCD) ha sido ampliamente utilizada como matriz ya que logra variar algunas de las propiedades desfavorables de los fármacos que incluyen, como por ejemplo, aumentar la solubilidad en agua y disminuir la toxicidad de muchas moléculas, entre otras múltiples ventajas. Existen diversos fármacos que presentan desventajas terapéuticas y que son candidatos a ser incluidos en matrices de βCD y transportados a través de sistemas nanopartículados, entre ellos 6-tioguanina (TG), 6-mercaptopurina (MP), melfalán (MF), 2-amino-4-(4-clorofenil)tiazol (AT) y feniletilamina, los cuales han sido estudiados en la presente tesis doctoral. Los complejos formados βCD-TG, βCD-MP, βCD-MF, βCD-AT y βCD-FEA en estado sólido y en solución se caracterizaron mediante difracción de rayos X de polvo, RMN de 1 (1H) y 2 dimensiones (ROESY). El proceso de inclusión deja fuera de la cavidad de βCD los grupos funcionales de los huéspedes que estabilizan NPsM que se depositaron a través de la técnica de pulverización catódica en alto vacío, formándose los sistemas ternarios βCD-TG-NPsAu, βCD-TG-NPsAg, βCD-MP-NPsAu, βCD-MFNPsAg, βCD-AT-NPsAu y βCD-FEA-NPsAu. Espectroscopia UV-visible en sólido mostró el plasmón de NPsAu y NPsAg, mediante SEM, FE-SEM, EDX y TEM se observó de manera directa la morfología de los cristales y de las NPsM obtenidas, que tienen un tamaño promedio de 20 nm de diámetro. Adicionalmente, el sistema ternario βCD-FEA-NPsAu fue caracterizado por espectroscopia IR y RAMAN que permitió analizar las interacciones del huésped al interior de la matriz, cuando forman el CI y los cambios generados por la presencia de las NPsAu. Los estudios mediante ROESY corroboran que FEA se desplaza parcialmente hacia fuera de la matriz debido a la interacción NH2-Au. Se cuantificó el porcentaje de cada componente del sistema ternario, evaluándose una alta capacidad de carga del fármaco, por otra parte, fue posible la liberación de FEA desde βCD-FEANPsAu de manera controlada a través de irradiación láser. Consideramos que un sistema único que posee dos componentes (NPsM y βCD) puede ser más eficiente en sus funciones para el transporte y la entrega de fármacosMetal nanoparticles (MNPs), specifically, gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs), exhibit excellent physical, chemical and biological properties, intrinsic to their nanometric size and have a direct application in the treatment of diseases. The nanosystems are designed to transport drugs, which can reach the site of action through various biological barriers. Thanks to the plasmon effect of the nanoparticles, it is possible promote the release of a drug into specific cells or tissues in a controlled manner through photothermal therapy. Another way to modify the physicochemical properties of a compound is through the formation of inclusion complexes (IC), which is based on unconventional interactions between a matrix and a guest. The βcyclodextrin (βCD) has been widely used as matrix, it is possible change some unfavorable properties of drugs including, for example, increase aqueous solubility and decrease toxicity of many molecules, among other advantages. There are several drugs that have therapeutic disadvantages, these may be included in matrices of βCD and may be transported through nanoparticulate systems, such as 6- thioguanine (TG), 6-mercaptopurine (MP), melphalan (MF), 2-amino-4- (4-chlorophenyl) thiazole (AT) and phenylethylamine (PhEA), which they have been studied in this doctoral thesis. The complexes βCD-TG, βCD-MP, βCD-MF, βCD-AT and βCD-PhEA in solid state and in solution using X-ray diffraction, 1 NMR (1H) and 2D (ROESY) were characterized. After of the inclusion process, the functional groups of the guests remain outside of the βCD cavity can stabilize MNPs, which they were deposited through the sputtering technique in high vacuum, forming the ternary systems βCD-TG-AuNPs, βCD-TGAgNPs, βCD-MP-AuNPs, βCD-MF-AgNPs, βCD-AT-AuNPs and βCD-PhEA-AuNPs. Using UV-Visible solid spectroscopy, the plasmons of AuNPs and AgNPs were observed , using SEM, FE-SEM, EDX and TEM, the morphology of the crystals and of the MNPs obtained were observed directly, these MNPs have an average size of 20 nm diameter. Additionally, the ternary system was characterized using IR and Raman spectroscopy. The interactions of the guest with the matrix, forming the IC and the changes brought about by the presence of NPsAu were observed. The partial displacement of PhEA outwardly of the matrix due to the NH2-Au interactions has been corroborated using ROESY studies. The percentage of each component in the ternary system was evaluated and a high capacity drug-loading was calculated. On the other hand, it was possible to release PhEA from βCD-PhEA-NPsAu of controlled manner using laser irradiation. We believe that a unique system, which has two components (MNPs and βCD) could be more efficient in its functions for the transportation and delivery of drugsConicyt, Fondecyt, Fonda

Label-free oligonucleotide-based SPR biosensor for the detection of the gene mutation causing prothrombin-related thrombophilia

Prothrombin-related thrombophilia is a genetic disorder produced by a substitution of a single DNA base pair, replacing guanine with adenine, and is detected mainly by polymerase chain reaction (PCR). A suitable alternative that could detect the single point mutation without requiring sample amplification is the surface plasmon resonance (SPR) technique. SPR biosensors are of great interest: they offer a platform to monitor biomolecular interactions, are highly selective, and enable rapid analysis in real time. Oligonucleotide-based SPR biosensors can be used to differentiate complementary sequences from partially complementary or noncomplementary strands. In this work, a glass chip covered with an ultrathin (50 nm) gold film was modified with oligonucleotide strands complementary to the mutated or normal (nonmutated) DNA responsible for prothrombin-related thrombophilia, forming two detection platforms called mutated thrombophilia (MT) biosensor and normal thrombophilia (NT) biosensor. The results show that the hybridization response is obtained in 30 min, label free and with high reproducibility. The sensitivity obtained in both systems was approximately 4 Delta mu RIU/nM. The dissociation constant and limits of detection calculated were 12.2 nM and 20 pM (3 fmol), respectively, for the MT biosensor, and 8.5 nM and 30 pM (4.5 fmol) for the NT biosensor. The two biosensors selectively recognize their complementary strand (mutated or normal) in buffer solution. In addition, each platform can be reused up to 24 times when the surface is regenerated with HCl. This work contributes to the design of the first SPR biosensor for the detection of prothrombin-related thrombophilia based on oligonucleotides with single point mutations, label-free and without the need to apply an amplification method.ANID-FONDECYT 3180706 1161225 ANID-FONDEQUIP EQM 140112 ANID-FONDAP 1513001

β-Cyclodextrin-Based Nanosponges Functionalized with Drugs and Gold Nanoparticles

Drugs are widely used as therapeutic agents; however, they may present some limitations. To overcome some of the therapeutic disadvantages of drugs, the use of β-cyclodextrin-based nanosponges (βCDNS) constitutes a promising strategy. βCDNS are matrices that contain multiple hydrophobic cavities, increasing the loading capacity, association, and stability of the included drugs. On the other hand, gold nanoparticles (AuNPs) are also used as therapeutic and diagnostic agents due to their unique properties and high chemical reactivity. In this work, we developed a new nanomaterial based on βCDNS and two therapeutic agents, drugs and AuNPs. First, the drugs phenylethylamine (PhEA) and 2-amino-4-(4-chlorophenyl)-thiazole (AT) were loaded on βCDNS. Later, the βCDNS–drug supramolecular complexes were functionalized with AuNPs, forming the βCDNS–PhEA–AuNP and βCDNS–AT–AuNP systems. The success of the formation of βCDNS and the loading of PhEA, AT, and AuNPs was demonstrated using different characterization techniques. The loading capacities of PhEA and AT in βCDNS were 90% and 150%, respectively, which is eight times higher than that with native βCD. The functional groups SH and NH2 of the drugs remained exposed and allowed the stabilization of the AuNPs, 85% of which were immobilized. These unique systems can be versatile materials with an efficient loading capacity for potential applications in the transport of therapeutic agents

Cyclodextrin-modified nanomaterials for drug delivery: Classification and advances in controlled release and bioavailability

In drug delivery, one widely used way of overcoming the biopharmaceutical problems present in several active pharmaceutical ingredients, such as poor aqueous solubility, early instability, and low bioavailability, is the formation of inclusion compounds with cyclodextrins (CD). In recent years, the use of CD derivatives in combination with nanomaterials has shown to be a promising strategy for formulating new, optimized systems. The goals of this review are to give in-depth knowledge and critical appraisal of the main CD-modified or CD-based nanomaterials for drug delivery, such as lipid-based nanocarriers, natural and synthetic polymeric nanocarriers, nanosponges, graphene derivatives, mesoporous silica nanoparticles, plasmonic and magnetic nanoparticles, quantum dots and other miscellaneous systems such as nanovalves, metal-organic frameworks, Janus nanoparticles, and nanofibers. Special attention is given to nanosystems that achieve controlled drug release and increase their bioavailability during in vivo studies.Fil: Real, Daniel Andrés. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Real, Daniel Andrés. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Bolaños, Karen. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Bolaños, Karen. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Bolaños, Karen. Universidad de Chile. Facultad de Medicina. Center for Studies on Exercise, Metabolism and Cancer. Cellular Communication Laboratory. Program of Cellular and Molecular Biology; Chile.Fil: Priotti, Josefina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Área Técnica Farmacéutica; Argentina.Fil: Yutronic, Nicolás. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química. Laboratorio de Nanoquímica y Química Supramolecular; Chile.Fil: Kogan, Marcelo J. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Kogan, Marcelo J. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Sierpe, Rodrigo. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Sierpe, Rodrigo. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Sierpe, Rodrigo. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química. Laboratorio de Nanoquímica y Química Supramolecular; Chile.Fil: Sierpe, Rodrigo. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Biosensores; Chile.Fil: Donoso González, Orlando. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química Farmacológica y Toxicológica. Laboratorio de Nanobiotecnología y Nanotoxicología; Chile.Fil: Donoso González, Orlando. Universidad de Chile and Pontificia Universidad Católica de Chile. Advanced Center for Chronic Diseases (ACCDiS); Chile.Fil: Donoso González, Orlando. Universidad de Chile. Facultad de Ciencias Químicas y Farmacéuticas. Departamento de Química. Laboratorio de Nanoquímica y Química Supramolecular; Chile

Solid-State Formation of a Potential Melphalan Delivery Nanosystem Based on β-Cyclodextrin and Silver Nanoparticles

Melphalan (Mel) is an antineoplastic widely used in cancer and other diseases. Its low solubility, rapid hydrolysis, and non-specificity limit its therapeutic performance. To overcome these disadvantages, Mel was included in β-cyclodextrin (βCD), which is a macromolecule that increases its aqueous solubility and stability, among other properties. Additionally, the βCD–Mel complex has been used as a substrate to deposit silver nanoparticles (AgNPs) through magnetron sputtering, forming the βCD–Mel–AgNPs crystalline system. Different techniques showed that the complex (stoichiometric ratio 1:1) has a loading capacity of 27%, an association constant of 625 M−1, and a degree of solubilization of 0.034. Added to this, Mel is partially included, exposing the NH2 and COOH groups that stabilize AgNPs in the solid state, with an average size of 15 ± 3 nm. Its dissolution results in a colloidal solution of AgNPs covered by multiple layers of the βCD–Mel complex, with a hydrodynamic diameter of 116 nm, a PDI of 0.4, and a surface charge of 19 mV. The in vitro permeability assays show that the effective permeability of Mel increased using βCD and AgNPs. This novel nanosystem based on βCD and AgNPs is a promising candidate as a Mel nanocarrier for cancer therapy

Molybdenum trioxide thin films doped with gold nanoparticles grown by a sequential methodology: photochemical metal-organic deposition (PMOD) and DC-magnetron sputtering

Gold nanoparticles (AuNPs) were deposited by DC-magnetron sputtering onto molybdenum trioxide (MoO3) thin films grown by Photochemical Metal-Organic Deposition (PMOD) on Si(100) and borosilicate glass substrates. The chemical, optical and morphology properties of the films were studied by UV/Vis Spectroscopy, Scanning Electron Microscopy (SEM), X-Ray Photoelectron Spectroscopy (XPS), and X-Ray Diffraction (XRD). SEM revealed that AuNPs formed after 5 s of sputtering. AuNPs are spherical and have both an average diameter of 18 nm and a relatively narrow size distribution. As the deposition time increases, larger structures are formed by an aggregation of AuNPs. XPS studies of the AuNP/MoO3 films on Si(100) showed the presence of Mo(VI) and Mo(V), which indicated that the films were primarily non-stoichiometric molybdenum oxides. The occurrence of oxygen vacancies in the substrate play an important role to stabilize the AuNP

Daidzein-Estrogen interaction in the rat uterus and its effect on human breast cancer cell growth

Sex hormone replacement therapy provides several advantages in the quality of life for climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of cancer development in these organs. The lower incidence of mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy isoflavones, including genistein. We have previously shown that genistein induces an estradiol-like hypertrophy of uterine cells, but does not induce cell proliferation, uterine eosinophilia, or endometrial edema. It also inhibits estradiol-induced mitosis in uterine cells and hormone-induced uterine eosinophilia and endometrial edema. Nevertheless, genistein stimulates growth of human breast cancer cells in culture; therefore, it is not an ideal estrogen for use in hormone replacement therapy (HRD). The present study investigated the effect of another soy isoflavone, daidzein (subcutaneous, 0.066 mg/kg body weight), in the

Optimizing Dacarbazine Therapy: Design of a Laser-Triggered Delivery System Based on β-Cyclodextrin and Plasmonic Gold Nanoparticles

Dacarbazine (DB) is an antineoplastic drug extensively used in cancer therapy. However, present limitations on its performance are related to its low solubility, instability, and non-specificity. To overcome these drawbacks, DB was included in β-cyclodextrin (βCD), which increased its aqueous solubility and stability. This new βCD@DB complex has been associated with plasmonic gold nanoparticles (AuNPs), and polyethylene glycol (PEG) has been added in the process to increase the colloidal stability and biocompatibility. Different techniques revealed that DB allows for a dynamic inclusion into βCD, with an association constant of 80 M−1 and a degree of solubilization of 0.023, where βCD showed a loading capacity of 16%. The partial exposure of the NH2 group in the included DB allows its interaction with AuNPs, with a loading efficiency of 99%. The PEG-AuNPs-βCD@DB nanosystem exhibits an optical plasmonic absorption at 525 nm, a surface charge of −29 mV, and an average size of 12 nm. Finally, laser irradiation assays showed that DB can be released from this platform in a controlled manner over time, reaching a concentration of 56 μg/mL (43% of the initially loaded amount), which, added to the previous data, validates its potential for drug delivery applications. Therefore, the novel nanosystem based on βCD, AuNPs, and PEG is a promising candidate as a new nanocarrier for DB

A surface functionalized with per-(6-amino-6-deoxy)-β-cyclodextrin for potential organic pollutant removal from water

In this work, we present a solid silicon substrate functionalized with modified beta-cyclodextrin monolayers as an optimal surface for organic contaminant uptake. The inclusion and capture of three potential pollutants, 4-chlorophenoxyacetic acid, 4-aminobenzoic acid and phenylethylamine, were studied. H-1-NMR and ROESY studies revealed the complete inclusion and details of the conformational orientation of the three guests in the per-(6-amino-6-deoxy)-beta-cyclodextrin matrix, forming three new inclusion complexes that have not yet been reported. Capture assays for the guests were carried out by immersing the substrates in an aqueous pollutant solution and by measuring the UV-vis spectra. This substrate showed a high sorption capacity at equilibrium, between 2.5x10(-5) and 6.0x10(-5) mmol/substrate, for the studied pollutants. In addition, this surface can be reused four times with an efficiency equal to the initial use. Therefore, it could be a versatile platform that could be applied for the capture of other organic pollutants from water.Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) CONICYT FONDECYT Projects PIA Anillo Millennium Nucleus Multifunctional Material for Surface Science Applications Comisión Nacional de Investigación Científica y Tecnológica (CONICYT