Browsing by Author "Kogan, Marcelo J."

Now showing 1 - 7 of 7
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    Differential Detection of Amyloid Aggregates in Old Animals Using Gold Nanorods by Computerized Tomography: A Pharmacokinetic and Bioaccumulation Study
    (2023) Jara-Guajardo, Pedro; Morales-Zavala, Francisco; Bolanos, Karen; Giralt, Ernest; Araya, Eyleen; Acosta, Gerardo A.; Albericio, Fernando; Alvarez, Alejandra R.; Kogan, Marcelo J.
    Introduction: The development of new materials and tools for radiology is key to the implementation of this diagnostic technique in clinics. In this work, we evaluated the differential accumulation of peptide-functionalized GNRs in a transgenic animal model (APPswe/PSENd1E9) of Alzheimer's disease (AD) by computed tomography (CT) and measured the pharmacokinetic parameters and bioaccumulation of the nanosystem.Methods: The GNRs were functionalized with two peptides, Ang2 and D1, which conferred on them the properties of crossing the blood-brain barrier and binding to amyloid aggregates, respectively, thus making them a diagnostic tool with great potential for AD. The nanosystem was administered intravenously in APPswe/PSEN1dE9 model mice of 4-, 8- and 18-months of age, and the accumulation of gold nanoparticles was observed by computed tomography (CT). The gold accumulation and biodistribution were determined by atomic absorption.Results: Our findings indicated that 18-month-old animals treated with our nanosystem (GNR-D1/Ang2) displayed noticeable differences in CT signals compared to those treated with a control nanosystem (GNR-Ang2). However, no such distinctions were observed in younger animals. This suggests that our nanosystem holds the potential to effectively detect AD pathology.Discussion: These results support the future development of gold nanoparticle-based technology as a more effective and accessible alternative for the diagnosis of AD and represent a significant advance in the development of gold nanoparticle applications in disease diagnosis.
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    Formation of Copper Nanoparticles Supported onto Inclusion Compounds of alpha-cyclodextrin: A New Route to Obtain Copper Nanoparticles
    (2010) Silva, Nataly; Moris, Silvana; Herrera Pisani, Bárbara Andrea; Diaz, Maximiliano; Kogan, Marcelo J.; Barrientos, Lorena; Yutronic, Nicolas; Jara, Paul
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    Functionalization of Gold Nanostars with Cationic β-Cyclodextrin-Based Polymer for Drug Co-Loading and SERS Monitoring
    (2021) Donoso-Gonzalez, Orlando; Lodeiro, Lucas; Aliaga, Alvaro E.; Laguna-Bercero, Miguel A.; Bollo, Soledad; Kogan, Marcelo J.; Yutronic, Nicolas; Sierpe, Rodrigo
    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 beta-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.
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    In vivo micro computed tomography detection and decrease in amyloid load by using multifunctionalized gold nanorods: a neurotheranostic platform for Alzheimer's disease
    (Royal Soc Chemistry, 2021) Morales Zavala, Francisco; Jara Guajardo, Pedro; Chamorro Veloso, David Daniel; Riveros, Ana L.; Chandia Cristi, América Valeska; Salgado Cortés, Nicole Andrea; Pismante, Paola; Giralt, Ernest; Sanchez Navarro, Macarena; Araya, Eyleen; Vasquez, Rodrigo; Acosta, Gerardo; Albericio, Fernando; Alvarez, Alejandra R.; Kogan, Marcelo J.
    The development and use of nanosystems is an emerging strategy for the diagnosis and treatment of a broad number of diseases, such as Alzheimer's disease (AD). Here, we developed a neurotheranostic nanosystem based on gold nanorods (GNRs) that works as a therapeutic peptide delivery system and can be detected in vivo for microcomputed tomography (micro-CT), being a diagnostic tool. GNRs functionalized with the peptides Ang2 (a shuttle to the Central Nervous System) and D1 (that binds to the A beta peptide, also inhibiting its aggregation) allowed detecting differences in vivo between wild type and AD mice (APPswe/PSEN1dE9) 15 minutes after a single dose by micro-CT. Moreover, after a recurrent treatment for one month with GNRs-D1/Ang2, we observed a diminution of amyloid load and inflammatory markers in the brain. Thus, this new designed nanosystem exhibits promising properties for neurotheranostics of AD.
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    Light-induced release of the cardioprotective peptide angiotensin-(1-9) from thermosensitive liposomes with gold nanoclusters
    (2020) Bejarano, Julian; Rojas, Aldo; Ramirez Sagredo, Andrea; Riveros, Ana L.; Morales Zavala, Francisco; Flores, Yvo; Riquelme, Jaime A.; Guzman, Fanny; Araya, Eyleen; Chiong, Mario; Ocaranza, María Paz; Morales, Javier O.; Villamizar Sarmiento, Maria Gabriela; Sanchez, Gina; Lavandero, Sergio; Kogan, Marcelo J.
    Angiotensin-(1-9), a component of the non-canonical renin-angiotensin system, has a short half-life in blood. This peptide has shown to prevent and/or attenuate hypertension and cardiovascular remodeling. A controlled release of angiotensin-(1-9) is needed for its delivery to the heart. Our aim was to develop a drug delivery system for angiotensin-(1-9). Thermosensitive liposomes (LipoTherm) were prepared with gold nanoclusters (LipoThermAuNC) to increase the stability and reach a temporal and spatial control of angiotensin-(1-9) release. Encapsulation efficiencies of nearly 50% were achieved in LipoTherm, reaching a total angiotensin-(1-9) loading of around 180 mu M. This angiotensin-(1-9)-loaded LipoTherm sized around 100 nm and exhibited a phase transition temperature of 43.C. AuNC were grown on LipoTherm and the new hybrid nanosystem showed energy absorption in the near-infrared (NIR) wavelength range. By NIR laser irradiation, a controlled release of angiotensin-(1-9) was achieved from the LipoTherm-AuNC nanosystem. These nanosystems did not show any cytotoxic effect on cultured cardiomyocytes. Biological activity of angiotensin-(1-9) released from the LipoTherm-AuNCbased nanosystem was confirmed using an ex vivo Langendorff heart model.
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    Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction : evolution toward prospective theranostic approaches
    (2018) Bejarano, Julian; Navarro-Marquez, Mario; Morales-Zavala, Francisco; Morales, Javier O.; Garcia-Carvajal, Ivonne; Araya-Fuentes, Eyleen; Flores, Yvo; Verdejo Pinochet, Hugo; Castro Gálvez, Pablo Federico; Lavandero, Sergio; Kogan, Marcelo J.
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    New Smoothened ligands based on the purine scaffold as potential agents for treating pancreatic cancer
    (2024) Espinosa-Bustos, Christian; Bertrand, Jeanluc; Villegas-Menares, Alondra; Guerrero, Simon; Di Marcotullio, Lucia; Navacci, Shirin; Schulte, Gunnar; Kozielewicz, Pawel; Bloch, Nicolas; Villela, Valentina; Paulino, Margot; Kogan, Marcelo J.; Cantero, Jorge; Salas, Cristian O.
    Aberrant activation of the Hedgehog (Hh) signalling pathway has been associated with the development and progression of pancreatic cancer. For this reason, blockade of Hh pathway by inhibitors targeting the G proteincoupled receptor Smoothened (SMO) has been considered as a therapeutic target for the treatment of this cancer. In our previous work, we obtained a new SMO ligand based on a purine scaffold (compound I), which showed interesting antitumor activity in several cancer cell lines. In this work, we report the design and synthesis of 17 new purine derivatives, some of which showed high cytotoxic effect on Mia-PaCa-2 (Hh-dependent pancreatic cancer cell lines) and low toxicity on non-neoplastic HEK-293 cells compared with gemcitabine, such as 8f, 8g and 8h (IC50 = 4.56, 4.11 and 3.08 mu M, respectively). Two of these purines also showed their ability to bind to SMO through NanoBRET assays (pKi = 5.17 for 8f and 5.01 for 8h), with higher affinities to compound I (pKi = 1.51). In addition, docking studies provided insight the purine substitution pattern is related to the affinity on SMO. Finally, studies of Hh inhibition for selected purines, using a transcriptional functional assay based on luciferase activity in NIH3T3 Shh-Light II cells, demonstrated that 8g reduced GLI activity with a IC50 = 6.4 mu M as well as diminished the expression of Hh target genes in two specific Hh-dependent cell models, Med1 cells and Ptch1- /- mouse embryonic fibroblasts. Therefore, our results provide a platform for the design of SMO ligands that could be potential selective cytotoxic agents for the treatment of pancreatic cancer.