Publications by authors named "Marcelo J Kogan"

100 Publications

Peptide Targeted Gold Nanoplatform Carrying miR-145 Induces Antitumoral Effects in Ovarian Cancer Cells.

Pharmaceutics 2022 Apr 28;14(5). Epub 2022 Apr 28.

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380000, Chile.

One of the recent attractive therapeutic approaches for cancer treatment is restoring downregulated microRNAs. They play an essential muti-regulatory role in cellular processes such as proliferation, differentiation, survival, apoptosis, cell cycle, angiogenesis, and metastasis, among others. In this study, a gold nanoplatform (GNPF) carrying miR-145, a downregulated microRNA in many cancer types, including epithelial ovarian cancer, was designed and synthesized. For targeting purposes, the GNPF was functionalized with the FSH33 peptide, which provided selectivity for ovarian cancer, and loaded with the miR-145 to obtain the nanosystem GNPF-miR-145. The GNPF-mir-145 was selectively incorporated in A2780 and SKOV3 cells and significantly inhibited cell viability and migration and exhibited proliferative and anchor-independent growth capacities. Moreover, it diminished VEGF release and reduced the spheroid size of ovarian cancer through the damage of cell membranes, thus decreasing cell viability and possibly activating apoptosis. These results provide important advances in developing miR-based therapies using nanoparticles as selective vectors and provide approaches for in vivo evaluation.
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http://dx.doi.org/10.3390/pharmaceutics14050958DOI Listing
April 2022

Surface enhanced fluorescence effect improves the in vivo detection of amyloid aggregates.

Nanomedicine 2022 May 17;44:102569. Epub 2022 May 17.

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380494, Chile; Advanced Center for Chronic Diseases (ACCDiS), Sergio Livingstone 1007, Independencia, Santiago 8380494, Chile. Electronic address:

The β-amyloid (Aβ) peptide is one of the key etiological agents in Alzheimer's disease (AD). The in vivo detection of Aβ species is challenging in all stages of the illness. Currently, the development of fluorescent probes allows the detection of Aβ 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 Aβ 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 Aβ using NIR probes in vivo.
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http://dx.doi.org/10.1016/j.nano.2022.102569DOI Listing
May 2022

Gold nanostructures: synthesis, properties, and neurological applications.

Chem Soc Rev 2022 Apr 4;51(7):2601-2680. Epub 2022 Apr 4.

Laser Research Center, University of Johannesburg, Doorfontein 2028, South Africa.

Recent advances in technology are expected to increase our current understanding of neuroscience. Nanotechnology and nanomaterials can alter and control neural functionality in both and experimental setups. The intersection between neuroscience and nanoscience may generate long-term neural interfaces adapted at the molecular level. Owing to their intrinsic physicochemical characteristics, gold nanostructures (GNSs) have received much attention in neuroscience, especially for combined diagnostic and therapeutic (theragnostic) purposes. GNSs have been successfully employed to stimulate and monitor neurophysiological signals. Hence, GNSs could provide a promising solution for the regeneration and recovery of neural tissue, novel neuroprotective strategies, and integrated implantable materials. This review covers the broad range of neurological applications of GNS-based materials to improve clinical diagnosis and therapy. Sub-topics include neurotoxicity, targeted delivery of therapeutics to the central nervous system (CNS), neurochemical sensing, neuromodulation, neuroimaging, neurotherapy, tissue engineering, and neural regeneration. It focuses on core concepts of GNSs in neurology, to circumvent the limitations and significant obstacles of innovative approaches in neurobiology and neurochemistry, including theragnostics. We will discuss recent advances in the use of GNSs to overcome current bottlenecks and tackle technical and conceptual challenges.
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http://dx.doi.org/10.1039/d1cs01111aDOI Listing
April 2022

Cyclodextrin-Modified Nanomaterials for Drug Delivery: Classification and Advances in Controlled Release and Bioavailability.

Pharmaceutics 2021 Dec 10;13(12). Epub 2021 Dec 10.

Laboratorio de Nanobiotecnología y Nanotoxicología, Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380544, Chile.

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.
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http://dx.doi.org/10.3390/pharmaceutics13122131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706493PMC
December 2021

NIR and glutathione trigger the surface release of methotrexate linked by Diels-Alder adducts to anisotropic gold nanoparticles.

Mater Sci Eng C Mater Biol Appl 2021 Dec 27;131:112512. Epub 2021 Oct 27.

Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, Chile. Electronic address:

The administration and controlled release of drugs over time remains one of the greatest challenges of science today. In the nanomaterials field, anisotropic gold nanoparticles (AuNPs) with plasmon bands centered at the near-infrared region (NIR), such as gold nanorods (AuNRs) and gold nanoprisms (AuNPrs), under laser irradiation, locally increase the temperature, allowing the release of drugs. In this sense, temporally controlled drug delivery could be promoted by external stimuli using thermo-reversible chemical reactions, such as Diels-Alder cycloadditions from a diene and a dienophile fragment (compound a). In this study, an antitumor drug (methotrexate, MTX) was linked to plasmonic AuNPs by a Diels-Alder adduct (compound c), which after NIR suffers a retro-Diels-Alder reaction, producing release of the drug (compound b). We obtained two nanosystems based on AuNRs and AuNPrs. Both nanoconstructs were coated with BSA-r (Bovine Serum Albumin functionalized with Arg, all-D octa arginine) in order to increase the colloidal stability and promote internalization of the nanosystems on HeLa and SK-BR-3 cells. In addition, the presence of BSA allows protecting the cargo from being released on the extracellular environment and promotes the photothermal release of the drug in the presence of glutathione (GSH). The nanosystems' drug release profile was evaluated after NIR irradiation in the presence and absence of glutathione (GSH), showing a considerable increase of drug release when NIR light and glutathione were combined. This work broadens the range of possibilities of using two complementary strategies for the controlled release of an antitumor drug from AuNRs and AuNPrs: the photothermal cleavage of a thermolabile adduct controlled by an external stimulus (laser irradiation), complemented with the use of the intracellular metabolite GSH.
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http://dx.doi.org/10.1016/j.msec.2021.112512DOI Listing
December 2021

Enhanced Cellular Uptake of H-Chain Human Ferritin Containing Gold Nanoparticles.

Pharmaceutics 2021 Nov 19;13(11). Epub 2021 Nov 19.

Department of Pharmacological and Toxicological Chemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago 8380494, Chile.

Gold nanoparticles (AuNP) capped with biocompatible layers have functional optical, chemical, and biological properties as theranostic agents in biomedicine. The ferritin protein containing in situ synthesized AuNPs has been successfully used as an effective and completely biocompatible nanocarrier for AuNPs in human cell lines and animal experiments in vivo. Ferritin can be uptaken by different cell types through receptor-mediated endocytosis. Despite these advantages, few efforts have been made to evaluate the toxicity and cellular internalization of AuNP-containing ferritin nanocages. In this work, we study the potential of human heavy-chain (H) and light-chain (L) ferritin homopolymers as nanoreactors to synthesize AuNPs and their cytotoxicity and cellular uptake in different cell lines. The results show very low toxicity of ferritin-encapsulated AuNPs on different human cell lines and demonstrate that efficient cellular ferritin uptake depends on the specific H or L protein chains forming the ferritin protein cage and the presence or absence of metallic cargo. Cargo-devoid apoferritin is poorly internalized in all cell lines, and the highest ferritin uptake was achieved with AuNP-loaded H-ferritin homopolymers in transferrin-receptor-rich cell lines, showing more than seven times more uptake than apoferritin.
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http://dx.doi.org/10.3390/pharmaceutics13111966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623468PMC
November 2021

Nanocrystal-based 3D-printed tablets: Semi-solid extrusion using melting solidification printing process (MESO-PP) for oral administration of poorly soluble drugs.

Int J Pharm 2022 Jan 20;611:121311. Epub 2021 Nov 20.

Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET, Córdoba, Argentina; Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, X5000XHUA Córdoba, Argentina. Electronic address:

This is the first report on the inclusion of nanocrystals (NCs) within 3D-printed oral solid dosage forms -3D-printed tablets or printlets- produced by the Melting Solidification Printing Process (MESO-PP) 3D printing technique. This method allowed the incorporation of albendazole (ABZ) nanocrystals in a concentration of up to 50% w/w, something not achieved in conventional tablets. An ink of PEG 1500/propylenegycol was used as a carrier and no physicochemical interactions or crystallinity modifications were observed due to the inclusion of ABZ-NCs into the ink, as demonstrated by TGA, DSC, XRD and FT-IR. In particular, the relative crystallinity of the ink loaded with NCs was 97.8% similar to the physical mixture of the components. Moreover, the presence of NCs was observed in the surface and matrix of the printlets by SEM. In addition, the printlet NCs demonstrated to be more effective than NCs included in hard gelatin capsules in improving drug dissolution in HCl 0.1 N. The particle size, crystallinity and chemical stability of the nanocrystals was maintained before and after 180 days of storage. Thus, these findings exhibit relevant pharmaceutical potential for developing stable, fast-release, oral, solid dosage forms of poorly soluble drugs combining 3D printing and nanocrystals. Additionally, this technique could be applied for printing objects using different types of nanocrystals embedded in low melting temperature polymers.
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http://dx.doi.org/10.1016/j.ijpharm.2021.121311DOI Listing
January 2022

Study of the interaction of folic acid-modified gold nanorods and fibrinogen through microfluidics: implications for protein adsorption, incorporation and viability of cancer cells.

Nanoscale 2021 Nov 4;13(42):17807-17821. Epub 2021 Nov 4.

Programa Institucional de Fomento a la I+D+I, Universidad Tecnológica Metropolitana, Ignacio Valdivieso 2409, San Joaquín, Chile.

Gold nanoparticles (GNPs) are an attractive nanomaterial for potential applications in therapy and diagnostics due to their capability to direct toward specific sites in the organism. However, when exposed to plasma, GNPs can interact with different biomolecules that form a dynamic nano-bio interface called a "protein corona" (PC). Remarkably, the PC could affect multiple biological processes, such as cell targeting and uptake, cytotoxicity, and nanoparticle (NP) clearance. The interaction of nanomaterials with plasmatic proteins has been widely studied under bulk conditions, however, under dynamic conditions, it has just recently been explored. Thus, to mimic a dynamic natural environment found in arteries and veins, microfluidic devices were used. In this work, gold nanorods (GNRs) were synthesized and conjugated with polyethylene glycol (PEG) to reduce their interaction with plasma proteins and increase their biocompatibility. Then, GNRs were functionalized with folic acid, a targeting ligand typically used to recognize tumor cells. The resulting nanosystem was exposed to fibrinogen (FB) to study the development and biological impact of PC formation through two strategies: bulk and laminar flow conditions. The obtained nanosystems were characterized by absorption spectrophotometry, DLS, laser Doppler microelectrophoresis, neutron activation analysis, circular dichroism spectroscopy and TEM. Finally, cell viability and cellular uptake assays were performed to study the influence of the PC on the cell viability and delivery of nanosystems.
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http://dx.doi.org/10.1039/d1nr03179aDOI Listing
November 2021

The curvature of gold nanoparticles influences the exposure of amyloid-β and modulates its aggregation process.

Mater Sci Eng C Mater Biol Appl 2021 Sep 23;128:112269. Epub 2021 Jun 23.

Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Chile; Advanced Center for Chronic Diseases (ACCDis), Chile. Electronic address:

Gold nanoparticles (GNP) are tunable nanomaterials that can be used to develop rational therapeutic inhibitors against the formation of pathological aggregates of proteins. In the case of the pathological aggregation of the amyloid-β protein (Aβ), the shape of the GNP can slow down or accelerate its aggregation kinetics. However, there is a lack of elementary knowledge about how the curvature of GNP alters the interaction with the Aβ peptide and how this interaction modifies key molecular steps of fibril formation. In this study, we analysed the effect of flat gold nanoprisms (GNPr) and curved gold nanospheres (GNS) on in vitro Aβ42 fibril formation kinetics by using the thioflavin-based kinetic assay and global fitting analysis, with several models of aggregation. Whereas GNPr accelerate the aggregation process and maintain the molecular mechanism of aggregation, GNS slow down this process and modify the molecular mechanism to one of fragmentation/secondary nucleation, with respect to controls. These results can be explained by a differential interaction between the Aβ peptide and GNP observed by Raman spectroscopy. While flat GNPr expose key hydrophobic residues involved in the Aβ peptide aggregation, curved GNS hide these residues from the solvent. Thus, this study provides mechanistic insights to improve the rational design of GNP nanomaterials for biomedical applications in the field of amyloid-related aggregation.
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http://dx.doi.org/10.1016/j.msec.2021.112269DOI Listing
September 2021

Oligoarginine Peptide Conjugated to BSA Improves Cell Penetration of Gold Nanorods and Nanoprisms for Biomedical Applications.

Pharmaceutics 2021 Aug 5;13(8). Epub 2021 Aug 5.

Advanced Center of Chronic Diseases (ACCDis), Santiago 8380494, Chile.

Gold nanoparticles (AuNPs) have been shown to be outstanding tools for drug delivery and biomedical applications, mainly owing to their colloidal stability, surface chemistry, and photothermal properties. The biocompatibility and stability of nanoparticles can be improved by capping the nanoparticles with endogenous proteins, such as albumin. Notably, protein coating of nanoparticles can interfere with and decrease their cell penetration. Therefore, in the present study, we functionalized albumin with the r peptide (All-D, octaarginine) and used it for coating NIR-plasmonic anisotropic gold nanoparticles. Gold nanoprisms (AuNPrs) and gold nanorods (AuNRs) were coated with bovine serum albumin (BSA) previously functionalized using a cell penetrating peptide (CPP) with the r sequence (BSA-r). The effect of the coated and r-functionalized AuNPs on HeLa cell viability was assessed by the MTS assay, showing a low effect on cell viability after BSA coating. Moreover, the internalization of the nanostructures into HeLa cells was assessed by confocal microscopy and transmission electron microscopy (TEM). As a result, both nanoconstructs showed an improved internalization level after being capped with BSA-r, in contrast to the BSA-functionalized control, suggesting the predominant role of CPP functionalization in cell internalization. Thus, our results validate both novel nanoconstructs as potential candidates to be coated by endogenous proteins and functionalized with a CPP to optimize cell internalization. In a further approach, coating AuNPs with CPP-functionalized BSA can broaden the possibilities for biomedical applications by combining their optical properties, biocompatibility, and cell-penetration abilities.
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http://dx.doi.org/10.3390/pharmaceutics13081204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400532PMC
August 2021

Extracellular Vesicles as Mediators of Cancer Disease and as Nanosystems in Theranostic Applications.

Cancers (Basel) 2021 Jul 2;13(13). Epub 2021 Jul 2.

Laboratorio de Comunicaciones Celulares, Centro de Estudios en Ejercicio, Metabolismo y Cáncer (CEMC), Programa de Biología Celular y Molecular, Facultad de Medicina, Universidad de Chile, Santiago 8380453, Chile.

Cancer remains a leading cause of death worldwide despite decades of intense efforts to understand the molecular underpinnings of the disease. To date, much of the focus in research has been on the cancer cells themselves and how they acquire specific traits during disease development and progression. However, these cells are known to secrete large numbers of extracellular vesicles (EVs), which are now becoming recognized as key players in cancer. EVs contain a large number of different molecules, including but not limited to proteins, mRNAs, and miRNAs, and they are actively secreted by many different cell types. In the last two decades, a considerable body of evidence has become available indicating that EVs play a very active role in cell communication. Cancer cells are heterogeneous, and recent evidence reveals that cancer cell-derived EV cargos can change the behavior of target cells. For instance, more aggressive cancer cells can transfer their "traits" to less aggressive cancer cells and convert them into more malignant tumor cells or, alternatively, eliminate those cells in a process referred to as "cell competition". This review discusses how EVs participate in the multistep acquisition of specific traits developed by tumor cells, which are referred to as "the hallmarks of cancer" defined by Hanahan and Weinberg. Moreover, as will be discussed, EVs play an important role in drug resistance, and these more recent advances may explain, at least in part, why pharmacological therapies are often ineffective. Finally, we discuss literature proposing the use of EVs for therapeutic and prognostic purposes in cancer.
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http://dx.doi.org/10.3390/cancers13133324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268753PMC
July 2021

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan.

Int J Mol Sci 2021 Jun 16;22(12). Epub 2021 Jun 16.

Departmento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Ñuñoa, Santiago 7800003, Chile.

This article describes the synthesis and characterization of β-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of laser irradiation. The NS-MPH and NS-CYT inclusion compounds were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), UV-Vis, and proton nuclear magnetic resonance (H-NMR). Thus, the inclusion of MPH and CYT inside the cavities of NSs was confirmed. The association of AuNPs with the ICs was confirmed by SEM, EDS, TEM, and UV-Vis. Drug release studies using NSs synthesized with different molar ratios of β-cyclodextrin and diphenylcarbonate (1:4 and 1:8) demonstrated that the ability of NSs to entrap and release the drug molecules depends on the crosslinking between the cyclodextrin monomers. Finally, irradiation assays using a continuous laser of 532 nm showed that photothermal drug release of both MPH and CYT from the cavities of NSs via plasmonic heating of AuNPs is possible.
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http://dx.doi.org/10.3390/ijms22126446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234497PMC
June 2021

Nanoparticle-Mediated Angiotensin-(1-9) Drug Delivery for the Treatment of Cardiac Hypertrophy.

Pharmaceutics 2021 Jun 1;13(6). Epub 2021 Jun 1.

Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Católica de Chile, Santiago 8380494, Chile.

Ang-(1-9) peptide is a bioactive vasodilator peptide that prevents cardiomyocyte hypertrophy in vitro and in vivo as well as lowers blood pressure and pathological cardiovascular remodeling; however, it has a reduced half-life in circulation, requiring a suitable carrier for its delivery. In this work, hybrid nanoparticles composed of polymeric nanoparticles (pNPs) based on Eudragit E/Alginate (EE/Alg), and gold nanospheres (AuNS), were developed to evaluate their encapsulation capacity and release of Ang-(1-9) under different experimental conditions. Hybrid pNPs were characterized by dynamic light scattering, zeta potential, transmission and scanning electron microscopy, size distribution, and concentration by nanoparticle tracking analysis. Nanometric pNPs, with good polydispersity index and colloidally stable, produced high association efficiency of Ang-(1-9) and controlled release. Finally, the treatment of neonatal cardiomyocytes in culture with EE/Alg/AuNS 2% + Ang-(1-9) 20% pNPs decreased the area and perimeter, demonstrating efficacy in preventing norepinephrine-induced cardiomyocyte hypertrophy. On the other hand, the incorporation of AuNS did not cause negative effects either on the cytotoxicity or on the association capacity of Ang-(1-9), suggesting that the hybrid carrier EE/Alg/AuNS pNPs could be used for the delivery of Ang-(1-9) in the treatment of cardiovascular hypertrophy.
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http://dx.doi.org/10.3390/pharmaceutics13060822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228229PMC
June 2021

In vivo micro computed tomography detection and decrease in amyloid load by using multifunctionalized gold nanorods: a neurotheranostic platform for Alzheimer's disease.

Biomater Sci 2021 Jun 13;9(11):4178-4190. Epub 2021 May 13.

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

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 Aβ 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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http://dx.doi.org/10.1039/d0bm01825bDOI Listing
June 2021

Plasmonic Nanoparticles as Optical Sensing Probes for the Detection of Alzheimer's Disease.

Sensors (Basel) 2021 Mar 16;21(6). Epub 2021 Mar 16.

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Dr. Carlos Lorca Tobar 964, Independencia, 8380000 Santiago, Chile.

Alzheimer's disease (AD), considered a common type of dementia, is mainly characterized by a progressive loss of memory and cognitive functions. Although its cause is multifactorial, it has been associated with the accumulation of toxic aggregates of the amyloid-β peptide (Aβ) and neurofibrillary tangles (NFTs) of tau protein. At present, the development of highly sensitive, high cost-effective, and non-invasive diagnostic tools for AD remains a challenge. In the last decades, nanomaterials have emerged as an interesting and useful tool in nanomedicine for diagnostics and therapy. In particular, plasmonic nanoparticles are well-known to display unique optical properties derived from their localized surface plasmon resonance (LSPR), allowing their use as transducers in various sensing configurations and enhancing detection sensitivity. Herein, this review focuses on current advances in in vitro sensing techniques such as Surface-enhanced Raman scattering (SERS), Surface-enhanced fluorescence (SEF), colorimetric, and LSPR using plasmonic nanoparticles for improving the sensitivity in the detection of main biomarkers related to AD in body fluids. Additionally, we refer to the use of plasmonic nanoparticles for in vivo imaging studies in AD.
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http://dx.doi.org/10.3390/s21062067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998661PMC
March 2021

The Influence of Size and Chemical Composition of Silver and Gold Nanoparticles on in vivo Toxicity with Potential Applications to Central Nervous System Diseases.

Int J Nanomedicine 2021 15;16:2187-2201. Epub 2021 Mar 15.

Department of Pharmacological and Toxicological Chemistry, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, Chile.

The physicochemical and optical properties of silver nanoparticles (SNPs) and gold nanoparticles (GNPs) have allowed them to be employed for various biomedical applications, including delivery, therapy, imaging, and as theranostic agents. However, since they are foreign body systems, they are usually redistributed and accumulated in some vital organs, which can produce toxic effects; therefore, this a crucial issue that should be considered for potential clinical trials. This review aimed to summarize the reports from the past ten years that have used SNPs and GNPs for in vivo studies on the diagnosis and treatment of brain diseases and those related to the central nervous system, emphasizing their toxicity as a crucial topic address. The article focuses on the effect of the nanoparticle´s size and chemical composition as relevant parameters for in vivo toxicity. At the beginning of this review, the general toxicity and distribution studies are discussed separately for SNPs and GNPs. Subsequently, this manuscript analyzes the principal applications of both kinds of nanoparticles for glioma, neurodegenerative, and other brain diseases, and discusses the advances in clinical trials. Finally, we analyze research prospects towards clinical applications for both types of metallic nanoparticles.
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http://dx.doi.org/10.2147/IJN.S260375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979359PMC
April 2021

Functionalization of Gold Nanostars with Cationic β-Cyclodextrin-Based Polymer for Drug Co-Loading and SERS Monitoring.

Pharmaceutics 2021 Feb 15;13(2). Epub 2021 Feb 15.

Laboratorio de Nanoquímica y Química Supramolecular, Departamento de Química, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Ñuñoa, Santiago 7800003, Chile.

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 β-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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http://dx.doi.org/10.3390/pharmaceutics13020261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919026PMC
February 2021

Microfluidics-assisted conjugation of chitosan-coated polymeric nanoparticles with antibodies: Significance in drug release, uptake, and cytotoxicity in breast cancer cells.

J Colloid Interface Sci 2021 Jun 13;591:440-450. Epub 2021 Feb 13.

Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara 44340, Mexico. Electronic address:

Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a polydimethylsiloxane (PDMS) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2), to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2 + breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties.
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http://dx.doi.org/10.1016/j.jcis.2021.02.031DOI Listing
June 2021

Functionalization with PEG/Angiopep-2 peptide to improve the delivery of gold nanoprisms to central nervous system: in vitro and in vivo studies.

Mater Sci Eng C Mater Biol Appl 2021 Feb 10;121:111785. Epub 2020 Dec 10.

Laboratorio de Nanobiotecnología y Nanotoxicología, Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile. Electronic address:

One of main drawbacks for the treatment of neurodegenerative pathologies is ensuring the delivery of therapeutic agents into the central nervous system (CNS). Nowadays, gold nanoprisms (GNPr) have become an emerging nanomaterial with a localized surface plasmon resonance in the biological window, showing applications in both detection and treatment of diseases. In this work, GNPr were functionalized with polyethylene glycol (PEG) and Angiopep-2 (Ang2) peptide to obtain a new highly stable nanomaterial and evaluate its toxicity and ability to cross the blood-brain barrier (BBB) in a zebrafish larvae model. The success in the functionalization was confirmed by a full characterization that showed the physicochemical changes at each step. In turn, the colloidal stability of GNPr-PEG-Ang2 in biologically relevant media also was demonstrated. The toxicity assays of GNPr-PEG-Ang2 performed on SH-SY5Y neuroblastoma cell line and on zebrafish larvae showed no effects both in vitro and in vivo. GNPr delivery to the CNS was studied in zebrafish larvae by immersion. We confirmed that functionalization with PEG-Ang2 improved the crossing through the BBB in this model compared with GNPr functionalized only with PEG. Notably, our nanomaterial was not detected in the CNS of zebrafish larvae 24 h after exposure that correlates with an adequate clearance of GNPr-PEG-Ang2 from the brain. This report is the first study of GNPr in the in vivo model of zebrafish larvae demonstrating that its functionalization with Ang2 allows the crossing of the BBB. Moreover, considering the stability achieved of the GNPr-PEG-Ang2 and the results of in vitro and in vivo studies, this work becomes a high contribution to the design of new nanomaterials with potential biomedical applications for CNS-related diseases.
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http://dx.doi.org/10.1016/j.msec.2020.111785DOI Listing
February 2021

The Combined Use of Gold Nanoparticles and Infrared Radiation Enables Cytosolic Protein Delivery.

Chemistry 2021 Mar 15;27(14):4670-4675. Epub 2021 Feb 15.

Institute for Research in Biomedicine, Barcelona Institute of, Science and Technology, Baldiri Reixac 10, 08028, Barcelona, Spain.

Cytosolic protein delivery remains elusive. The inability of most proteins to cross the cellular membrane is a huge hurdle. Here we explore the unique photothermal properties of gold nanorods (AuNRs) to trigger cytosolic delivery of proteins. Both partners, protein and AuNRs, are modified with a protease-resistant cell-penetrating peptide with nuclear targeting properties to induce internalization. Once internalized, spatiotemporal control of protein release is achieved by near-infrared laser irradiation in the safe second biological window. Importantly, catalytic amounts of AuNRs are sufficient to trigger cytosolic protein delivery. To the best of our knowledge, this is the first time that AuNRs with their maximum of absorption in the second biological window are used to deliver proteins into the intracellular space. This strategy represents a powerful tool for the cytosolic delivery of virtually any class of protein.
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http://dx.doi.org/10.1002/chem.202005000DOI Listing
March 2021

Poly-ε-caprolactone Nanoparticles Loaded with 4-Nerolidylcatechol (4-NC) for Growth Inhibition of .

Antibiotics (Basel) 2020 Dec 11;9(12). Epub 2020 Dec 11.

Department of Drugs and Medicines, School of Pharmaceutical Sciences, School of Pharmaceutical Sciences of São Paulo State University (UNESP), Rodovia Araraquara-Jaú, Km 1, Araraquara, SP 14800-903, Brazil.

Dermatophyte fungal infections are difficult to treat because they need long-term treatments. 4-Nerolidylcatechol (4-NC) is a compound found in that has been reported to demonstrate significant antifungal activity, but is easily oxidizable. Due to this characteristic, the incorporation in nanostructured systems represents a strategy to guarantee the compound's stability compared to the isolated form and the possibility of improving antifungal activity. The objective of this study was to incorporate 4-NC into polymeric nanoparticles to evaluate, in vitro and in vivo, the growth inhibition of . 4-NC was isolated from fresh leaves of and polymer nanoparticles of polycaprolactone were developed by nanoprecipitation using a 1:5 weight ratio (drug:polymer). Nanoparticles exhibited excellent encapsulation efficiency, and the antifungal activity was observed in nanoparticles with 4-NC incorporated. Polymeric nanoparticles can be a strategy employed for decreased cytotoxicity, increasing the stability and solubility of substances, as well as improving the efficacy of 4-NC.
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http://dx.doi.org/10.3390/antibiotics9120894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763452PMC
December 2020

Light-induced release of the cardioprotective peptide angiotensin-(1-9) from thermosensitive liposomes with gold nanoclusters.

J Control Release 2020 12 4;328:859-872. Epub 2020 Nov 4.

Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceúticas & Facultad Medicina, Universidad de Chile, Santiago 8380492, Chile; Departamento de Química Farmacológica y Toxicológica, Facultad Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380492, Chile; Corporación Centro de Estudios Científicos de las Enfermedades Crónicas (CECEC), Santiago 7680201, Chile. Electronic address:

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 (LipoTherm-AuNC) 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 μM. 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-AuNC-based nanosystem was confirmed using an ex vivo Langendorff heart model.
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http://dx.doi.org/10.1016/j.jconrel.2020.11.002DOI Listing
December 2020

Label-Free Oligonucleotide-Based SPR Biosensor for the Detection of the Gene Mutation Causing Prothrombin-Related Thrombophilia.

Sensors (Basel) 2020 Oct 31;20(21). Epub 2020 Oct 31.

Laboratorio de Biosensores, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile; Santos Dumont N° 964, Independencia, Santiago 8380492, Chile.

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 ΔμRIU/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.
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http://dx.doi.org/10.3390/s20216240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663036PMC
October 2020

Exploiting the Natural Properties of Extracellular Vesicles in Targeted Delivery towards Specific Cells and Tissues.

Pharmaceutics 2020 Oct 26;12(11). Epub 2020 Oct 26.

Advanced Center for Chronic Diseases (ACCDiS), University of Chile, Santos Dumont 964 Independencia, 8380000 Santiago, Chile.

Extracellular vesicles (EVs) are important mediators of intercellular communication that participate in many physiological/pathological processes. As such, EVs have unique properties related to their origin, which can be exploited for drug delivery applications in cell regeneration, immunosuppression, inflammation, cancer treatment or cardioprotection. Moreover, their cell-like membrane organization facilitates uptake and accumulation in specific tissues and organs, which can be exploited to improve selectivity of cargo delivery. The combination of these properties with the inclusion of drugs or imaging agents can significantly improve therapeutic efficacy and selectivity, reduce the undesirable side effects of drugs or permit earlier diagnosis of diseases. In this review, we will describe the natural properties of EVs isolated from different cell sources and discuss strategies that can be applied to increase the efficacy of targeting drugs or other contents to specific locations. The potential risks associated with the use of EVs will also be addressed.
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http://dx.doi.org/10.3390/pharmaceutics12111022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692617PMC
October 2020

Intranasal administration of gold nanoparticles designed to target the central nervous system: Fabrication and comparison between nanospheres and nanoprisms.

Int J Pharm 2020 Nov 6;590:119957. Epub 2020 Oct 6.

Laboratory for Biopharmaceutics, Department of Biomedical Engineering, Ben Gurion University of the Negev, E.D. Bergmann Campus, Be'er Sheva 84105, Israel. Electronic address:

The presence of the blood-brain barrier (BBB) limit gold nanoparticles (GNP) accumulation in central nervous system (CNS) after intravenous (IV) administration. The intranasal (IN) route has been suggested as a good strategy for circumventing the BBB. In this report, we used gold nanoprisms (78 nm) and nanospheres (47 nm), of comparable surface areas (8000 vs 7235 nm) functionalized with a polyethylene glycol (PEG) and D1 peptide (GNPr-D1 and GNS-D1, respectively) to evaluate their delivery to the CNS after IN administration. Cell viability assay showed that GNPr-D1 and GNS-D1 were not cytotoxic at concentrations ranged between 0.05 and 0.5 nM. IN administration of GNPr-D1 and GNS-D1 demonstrated a significant difference between the two types of GNP, in which the latter reached the CNS in higher levels. Pharmacokinetic study showed that the peak brain level of gold was 0.75 h after IN administration of GNS-D1. After IN and IV administrations of GNS-D1, gold concentrations found in brain were 55 times higher via the IN route compared to IV administration. Data revealed that the IN route is more effective for targeting gold to the brain than IV administration. Finally, no significant difference was observed between the IN and IV routes in the distribution of GNS-D1 in the various brain areas.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119957DOI Listing
November 2020

Adsorption of bovine serum albumin on gold nanoprisms: interaction and effect of NIR irradiation on protein corona.

J Mater Chem B 2020 09;8(37):8644-8657

Advanced Center for Chronic Diseases (ACCDiS), Santos Dumont 964, Independencia, Santiago, Chile and Departamento de Ciencias Químicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Av. Republica 275, Santiago, Chile.

Because of their photothermal properties, gold nanoparticles (AuNPs) have gained attention regarding their use in drug delivery and therapeutic applications. In this sense, it is interesting to consider their interactions with biologically available proteins, such as serum albumin, as well as the effects of irradiation and photothermal conversion on the protein structure that can lead to a loss of function or generate an immune response. Gold nanoprisms (AuNPrs) have gained interest due to their low toxicity, ease of synthesis, and excellent stability, promoting their use in bioapplications such as surface-enhanced Raman spectroscopy (SERS), drug delivery, and photothermal therapy. The interaction between AuNPrs, with plasmon bands centred in the near-infrared region (NIR), and bovine serum albumin (BSA) has not been explored yet. UV-Vis spectroscopy, dynamic light scattering (DLS) and fluorescence spectroscopy were used to study the interaction between AuNPrs and BSA in addition to estimation of the adsorption rate and kinetic and thermodynamic parameters (K, ΔH°, ΔG°, ΔS°, and Ea) using adsorption isotherms and Langmuir and Freundlich models. The results suggest spontaneous cooperative binding in multilayer adsorption, achieved by the chemisorption of BSA on the AuNPr surface through the S-Au interaction, as confirmed by Raman spectroscopy. On the other hand, the photothermal conversion efficiency (PE) of the coated nanoparticles after NIR irradiation was assessed, resulting in a slight decrease in the PE of BSA coated on AuNPrs in comparison with that of noncapped nanoparticles. The effect of the irradiation on the protein conformation of capped nanoparticles was also assessed; circular dichroism showed BSA unfolding upon interaction with AuNPrs, with a decrease in the α-helix and β-sheet contents, as well as an increase in random coil conformations. Changes in the Raman spectrum suggest a modification of the disposition of the protein residues exposed to the gold surface after NIR irradiation; but at the secondary structure level, no relevant changes were observed. This provides possibilities for the use of NPs-BSA for bioapplications based on the photothermal effect promoted by laser irradiation, since the biological identity of the protein is preserved after NIR irradiation.
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http://dx.doi.org/10.1039/d0tb01246gDOI Listing
September 2020

Inhibition of chymotrypsin-like activity of the proteasome by ixazomib prevents mitochondrial dysfunction during myocardial ischemia.

PLoS One 2020 26;15(5):e0233591. Epub 2020 May 26.

Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

The heart is critically dependent on mitochondrial respiration for energy supply. Ischemia decreases oxygen availability, with catastrophic consequences for cellular energy systems. After a few minutes of ischemia, the mitochondrial respiratory chain halts, ATP levels drop and ion gradients across cell membranes collapse. Activation of cellular proteases and generation of reactive oxygen species by mitochondria during ischemia alter mitochondrial membrane permeability, causing mitochondrial swelling and fragmentation and eventually cell death. The mitochondria, therefore, are important targets of cardioprotection against ischemic injury. We have previously shown that ixazomib (IXA), a proteasome inhibitor used for treating multiple myeloma, effectively reduced the size of the infarct produced by global ischemia in isolated rat hearts and prevented degradation of the sarcoplasmic reticulum calcium release channel RyR2. The aim of this work was to further characterize the protective effect of IXA by determining its effect on mitochondrial morphology and function after ischemia. We also quantified the effect of IXA on levels of mitofusin-2, a protein involved in maintaining mitochondrial morphology and mitochondria-SR communication. We found that mitochondria were significantly preserved and functional parameters such as oxygen consumption, the ability to generate a membrane potential, and glutathione content were improved in mitochondria isolated from hearts perfused with IXA prior to ischemia. IXA also blocked the release of cytochrome c observed in ischemia and significantly preserved mitofusin-2 integrity. These beneficial effects resulted in a significant decrease in the left ventricular end diastolic pressure upon reperfusion and a smaller infarct in isolated hearts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233591PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250417PMC
August 2020

Chitosan-Based Nanoparticles for Intracellular Delivery of ISAV Fusion Protein cDNA into Melanoma Cells: A Path to Develop Oncolytic Anticancer Therapies.

Mediators Inflamm 2020 29;2020:8680692. Epub 2020 Apr 29.

Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile (USACH), Alameda, 3363 Santiago, Chile.

Oncolytic virus therapy has been tested against cancer in preclinical models and clinical assays. Current evidence shows that viruses induce cytopathic effects associated with fusogenic protein-mediated syncytium formation and immunogenic cell death of eukaryotic cells. We have previously demonstrated that tumor cell bodies generated from cells expressing the fusogenic protein of the infectious salmon anemia virus (ISAV-F) enhance crosspriming and display prophylactic antitumor activity against melanoma tumors. In this work, we evaluated the effects of the expression of ISAV-F on the B16 melanoma model, both and , using chitosan nanoparticles as transfection vehicle. We confirmed that the transfection of B16 tumor cells with chitosan nanoparticles (NP-ISAV) allows the expression of a fusogenically active ISAV-F protein and decreases cell viability because of syncytium formation . However, the transfection induces a delay in tumor growth, without inducing changes on the lymphoid populations in the tumor and the spleen. Altogether, our observations show that expression of ISAV fusion protein using chitosan nanoparticles induces cell fusion in melanoma cells and slight antitumor response.
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http://dx.doi.org/10.1155/2020/8680692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206890PMC
July 2021

Gold Nanoparticles Mediate Improved Detection of β-amyloid Aggregates by Fluorescence.

Nanomaterials (Basel) 2020 Apr 6;10(4). Epub 2020 Apr 6.

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8380494, Chile.

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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http://dx.doi.org/10.3390/nano10040690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221977PMC
April 2020

Improving Cell Penetration of Gold Nanorods by Using an Amphipathic Arginine Rich Peptide.

Int J Nanomedicine 2020 17;15:1837-1851. Epub 2020 Mar 17.

Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

Introduction: Gold nanorods are highly reactive, have a large surface-to-volume ratio, and can be functionalized with biomolecules. Gold nanorods can absorb infrared electromagnetic radiation, which is subsequently dispersed as local heat. Gold nanoparticles can be used as powerful tools for the diagnosis and therapy of different diseases. To improve the biological barrier permeation of nanoparticles with low cytotoxicity, in this study, we conjugated gold nanorods with cell-penetrating peptides (oligoarginines) and with the amphipathic peptide CLPFFD.

Methods: We studied the interaction of the functionalized gold nanorods with biological membrane models (liposomes) by dynamic light scattering, transmission electron microscopy and the Langmuir balance. Furthermore, we evaluated the effects on cell viability and permeability with an MTS assay and TEM.

Results And Discussion: The interaction study by DLS, the Langmuir balance and cryo-TEM support that GNR-ArgCLPFFD enhances the interactions between GNRs and biological membranes. In addition, cells treated with GNR-ArgCLPFFD internalized 80% more nanoparticles than cells treated with GNR alone and did not induce cell damage.

Conclusion: Our results indicate that incorporation of an amphipathic sequence into oligoarginines for the functionalization of gold nanorods enhances biological membrane nanoparticle interactions and nanoparticle cell permeability with respect to nanorods functionalized with oligoarginine. Overall, functionalized gold nanorods with amphipathic arginine rich peptides might be candidates for improving drug delivery by facilitating biological barrier permeation.
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http://dx.doi.org/10.2147/IJN.S237820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090188PMC
July 2020
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