Browsing by Author "Kogan, Marcelo J."
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Publication Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic β‑Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field(2024) SALAZAR SANDOVAL, SEBASTIAN ANDRES; Díaz-Saldívar, Patricia; Araya, Ingrid; Celis, Freddy; Cortés-Arriagada, Diego; Riveros, Ana; Rojas-Romo, Carlos; Jullian, Carolina; Silva, Nataly; Yutronic, Nicolás; Kogan, Marcelo J.; Jara, Paulβ-cyclodextrin (β-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the “Atkinson−Brezovich criterion”. The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.Item Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking.(2019) Ezquer, Fernando; Quintanilla, María Elena; Morales, Paola; Santapau, Daniela; Ezquer, Marcelo; Kogan, Marcelo J.; Salas-Huenuleo, Edison; Herrera-Marschitz, Mario; Israel, YedyChronic ethanol consumption leads to brain oxidative stress and neuroinflammation, conditions known to potentiate and perpetuate each other. Several studies have shown that neuroinflammation results in increases in chronic ethanol consumption. Recent reports showed that the intra-cerebroventricular administration of mesenchymal stem cells to rats consuming alcohol chronically markedly inhibited oxidative-stress, abolished neuroinflammation and greatly reduced chronic alcohol intake and post deprivation relapselike alcohol intake. However, the intra-cerebroventricular administration of living cells is not suitable as a treatment of a chronic condition. The present study aimed at inhibiting ethanol intake by the noninvasive intranasal administration of human mesenchymal stem cell products: exosomes; microvesicles (40 to 150 nm) with marked antioxidant activity extruded from mesenchymal stem cells. The exosome membrane can fuse with the plasma membrane of cells in different tissues, thus delivering their content intracellularly. The study showed that the weekly intranasal administration of mesenchymal stem cell-derived exosomes to rats consuming alcohol chronically (i) inhibited their ethanol intake by 80% and blunted the relapselike “binge” drinking that follows an alcohol deprivation period and ethanol re-access. (ii) Intranasally administered exosomes were found in the brain within 24-hours; (iii) fully reversed both alcohol-induced hippocampal oxidative-stress, evidenced by a lower ratio of oxidized to reduced glutathione, and neuroinflammation, shown by a reduced astrocyte activation and microglial density and (iv) increased glutamate transporter GLT1 expression in nucleus accumbens, counteracting the inhibition of glutamate transporter activity, reportedly depressed under oxidative-stress conditions. Possible translational implications are envisagedPublication Synthesis and characterization of magnetite/gold core shell nanoparticles stabilized with a -cyclodextrin nanosponge to develop a magneto-plasmonic system(2023) Salazar Sandoval, Sebastián; Santibáñez, Daniel; Riveros, Ana; Araneda, Fabián; Bruna, Tamara; Silva, Nataly; Yutronic, Nicolás; Kogan, Marcelo J.; Jara, PaulMagnetite/gold core-shell nanoparticles (magnetite/gold NPs) have important optical and magnetic properties that provide potential for applications, especially biomedical ones. However, their preparation is not exempt from difficulties that might lead to unexpected or undesired structures. This work reports the synthesis and characterization of magnetite/gold NPs using tetramethylammonium hydroxide (TMAH) to promote the formation of a continuous interface between the magnetite core and the thin gold shell. The synthesized magnetite/gold NPs were characterized using transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), field emission scanning electron microscope (FE-SEM), ζ-potential, vibrating sample magnetometer (VSM), selected area electron diffraction (SAED), UV-Visible spectroscopy, and dynamic light scattering (DLS), confirming the core-shell structure of the NPs with narrow size distribution while evidencing its plasmonic and superparamagnetic properties as well. Further, the magnetite/gold NPs were associated and stabilized with a β-cyclodextrin nanosponge (β-CDNSs), obtaining a versatile magneto-plasmonic system for potential applications in the encapsulation and controlled release of drugs.Publication Synthesis of dumbbell-like heteronanostructures encapsulated in ferritin protein: Towards multifunctional protein based opto-magnetic nanomaterials for biomedical theranostic(2025) Moglia, Italo; Santiago, Margarita; Arellano, Andreas; SALAZAR SANDOVAL, SEBASTIAN ANDRES; Olivera-Nappa, Alvaro; Kogan, Marcelo J.; Soler, MónicaDumbbell-like hetero nanostructures based on gold and iron oxides is a promising material for biomedical applications, useful as versatile theranostic agents due the synergistic effect of their optical and magnetic properties. However, achieving precise control on their morphology, size dispersion, colloidal stability, biocompatibility and cell targeting remains as a current challenge. In this study, we address this challenge by employing biomimetic routes, using ferritin protein nanocages as template for these nanoparticles’ synthesis. We present the development of an opto-magnetic nanostructures using the ferritin protein, wherein gold and iron oxide nanostructures were produced within its cavity. Initially, we investigated the synthesis of gold nanostructures within the protein, generating clusters and plasmonic nanoparticles. Subsequently, we optimized the conditions for the superparamagnetic nanoparticles synthesis through controlled iron oxidation, thereby enhancing the magnetic properties of the resulting system. Finally, we produce magnetic nanoparticles in the protein with gold clusters, achieving the coexistence of both nanostructures within a single protein molecule, a novel material unprecedented to date. We observed that factors such as temperature, metal/protein ratios, pH, dialysis, and purification processes all have an impact on protein recovery, loading efficiency, morphology, and nanoparticle size. Our findings highlight the development of ferritin-based nanomaterials as versatile platforms for potential biomedical use as multifunctional theranostic agents.Publication β-Cyclodextrin nanosponges inclusion compounds associated with silver nanoparticles to increase the antimicrobial activity of quercetin(2023) Salazar Sandoval, Sebastián; Bruna, Tamara; Maldonado-Bravo, Francisca; Bolaños, Karen; Adasme-Reyes, Sofía; Riveros, Ana; Caro, Nelson; Yutronic, Nicolás; Silva, Nataly; Kogan, Marcelo J.; Jara, PaulThis work aimed to synthesize and characterize a nanocarrier that consisted of a ternary system, namely β-cyclodextrin-based nanosponge (NS) inclusion compounds (ICs) associated with silver nanoparticles (AgNPs) to increase the antimicrobial activity of quercetin (QRC). The nanosystem was developed to overcome the therapeutical limitations of QRC. The host–guest interaction between NSs and QRC was confirmed by field emission scanning electron microscopy (FE–SEM), X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), and proton nuclear magnetic resonance (1H–NMR). Moreover, the association of AgNPs with the NS–QRC was characterized using FE–SEM, energy-dispersive spectroscopy (EDS), transmission electron microscopy (TEM), dynamic light scattering (DLS), ζ-potential, and UV–Vis. Finally, the antimicrobial activity of the novel formulations was tested, which depicted that the complexation of QRC inside the supramolecular interstices of NSs increases the inhibitory effects against Escherichia coli ATCC25922, as compared to that observed in the free QRC. In addition, at the same concentrations used to generate an antibacterial effect, the NS–QRC system with AgNPs does not affect the metabolic activity of GES–1 cells. Therefore, these results suggest that the use of NSs associated with AgNPs resulted in an efficient strategy to improve the physicochemical features of QRC.