Browsing by Author "Jara-Guajardo, Pedro"

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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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    Gold Nanoparticles Mediate Improved Detection of β-amyloid Aggregates by Fluorescence
    (2020) Jara-Guajardo, Pedro; Cabrera, Pablo; Celis, Freddy; Soler, Monica; Berlanga, Isadora; Parra-Munoz, Nicole; Acosta, Gerardo; Albericio, Fernando; Guzman, Fanny; Campos, Marcelo; Alvarez, Alejandra; Morales-Zavala, Francisco; Kogan, Marcelo J.
    The early detection of the amyloid beta peptide aggregates involved in Alzheimer's disease is crucial to test new potential treatments. In this research, we improved the detection of amyloid beta peptide aggregates in vitro and ex vivo by fluorescence combining the use of CRANAD-2 and gold nanorods (GNRs) by the surface enhancement fluorescence effect. We synthetized GNRs and modified their surface with HS-PEG-OMe and HS-PEG-COOH and functionalized them with the D1 peptide, which has the capability to selectively bind to amyloid beta peptide. For an in vitro detection of amyloid beta peptide, we co-incubated amyloid beta peptide aggregates with the probe CRANAD-2 and GNR-PEG-D1 observing an increase in the intensity of the fluorescence signal attributed to surface enhancement fluorescence. Furthermore, the surface enhancement fluorescence effect was observed in brain slices of transgenic mice with Alzheimer's disease co-incubated with CRANAD-2 and GNR-PEG-D1. An increase in the fluorescence signal was observed allowing the detection of aggregates that cannot be detected with the single use of CRANAD-2. Gold nanoparticles allowed an improvement in the detection of the amyloid aggregated by fluorescence in vitro and ex vivo.
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    Surface enhanced fluorescence effect improves the in vivo detection of amyloid aggregates
    (2022) Cabrera, Pablo; Jara-Guajardo, Pedro; Oyarzun, Maria Paz; Parra-Munoz, Nicole; Campos, Aldo; Soler, Monica; Alvarez, Alejandra; Morales-Zavala, Francisco; Araya, Eyleen; Minniti, Alicia N.; Aldunate, Rebeca; Kogan, Marcelo J.
    The beta-amyloid (A beta) peptide is one of the key etiological agents in Alzheimer's disease (AD). The in vivo detection of A beta species is challenging in all stages of the illness. Currently, the development of fluorescent probes allows the detection of A beta in animal models in the near-infrared region (NIR). However, considering future applications in biomedicine, it is relevant to develop strategies to improve detection of amyloid aggregates using NIR probes. An innovative approach to increase the fluorescence signal of these fluorophores is the use of plasmonic gold nanoparticles (surface-enhanced fluorescence effect). In this work, we improved the detection of A beta aggregates in C. elegans and mouse models of AD by co-administering functionalized gold nanorods (GNRs-PEG-D1) with the fluorescent probes CRANAD-2 or CRANAD-58, which bind selectively to different amyloid species (soluble and insoluble). This work shows that GNRs improve the detection of A beta using NIR probes in vivo. (C) 2022 Published by Elsevier Inc.
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    The Cervical and Meningeal Lymphatic Network as a Pathway for Retrograde Nanoparticle Transport to the Brain
    (2024) Ramos-Zaldivar, Hector; Polakovicova, Iva; Salas-Huenuleo, Edison; Yefi, Claudia P.; Silva-Ancahuail, David; Jara-Guajardo, Pedro; Oyarzun, Juan Esteban; Neira-Troncoso, Alvaro; Burgos, Patricia, V; Cavieres, Viviana A.; Arias-Munoz, Eloisa; Martinez, Carlos; Riveros, Ana L.; Corvalan, Alejandro H.; Kogan, Marcelo J.; Andia, Marcelo E.
    Introduction: The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain. Methods: We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis. Results: Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures. Discussion: The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.