Improving Gold Nanorod Delivery to the Central Nervous System By Conjugation to the Shuttle Angiopep-2

Velasco-Aguirre, C.; Morales-Zavala, Francisco; Salas-Huenuleo, Edison; Gallardo-Toledo, Eduardo; Andonie, O.; Muñoz, Lorena; Rojas, Ximena; Acosta, Gerardo; Sánchez‐Navarro, Macarena; Giralt, Ernest; Araya, Eyleen; Alberício, Fernando; Kogan, Marcelo J.

doi:10.2217/nnm-2017-0181

Cited by 42 publications

(25 citation statements)

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“…Citrate-coated gold nanoparticles were synthetized as described in methods and subsequently two types of thiol PEGs (methylated and carboxylated) were chemisorbed on their surface. The methylated PEG contributes to the colloidal stabilization [45], while the carboxylated PEG permits conjugation with folic acid [43,46] following an EDC/NHS protocol. For the nanoparticles, a plasmonic peak of light absorption at 520 nm and an average size of 12 nm with a peak at 13 nm were observed by UV-visible spectroscopy and electron transmission microscopy, respectively (Fig.…”

Section: Synthesis and Characterization Of Aunp-peg-famentioning

confidence: 99%

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors

Lara¹,

Palma-Florez²,

Salas-Huenuleo³

et al. 2020

J Nanobiotechnol

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Background: Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy. Results: We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules.

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Section: Synthesis and Characterization Of Aunp-peg-famentioning

confidence: 99%

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors

Lara¹,

Palma-Florez²,

Salas-Huenuleo³

et al. 2020

J Nanobiotechnol

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“…Gold nanoparticles (Au-NPs) are nanomaterials that have received much attention due to their physical and chemical properties that make them particularly attractive for biomedical applications [ 1 ]. When Au-NPs are irradiated at a specific wavelength, local energy is released as heat, a Surface Plasmon Resonance (SPR) phenomenon referred to as the “photothermal effect” [ 2 , 3 , 4 , 5 ]. Due to this effect, gold nanostructures have the potential to kill cancer cells, to disaggregate amyloid plaques in Alzheimer disease, and also to release molecules in a spatio-temporal manner [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…The most commonly used gold nanostructures are nanospheres (GNS), with an SPR absorption peak around 510 and 540 nm [ 2 , 10 ]. In terms of biological applications, gold nanostructures with the plasmon absorption in the NIR region, also called “NIR window” or “transparent region” (between 700 and 1100 nm) often are preferable, because the radiation of longer wavelength can penetrate human tissues without causing any damage to the organism [ 3 , 4 ]. Interestingly, gold nanorods (GNR) can be synthesized in a manner that permits adjusting their SPR to the required biological NIR window [ 3 , 4 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…In terms of biological applications, gold nanostructures with the plasmon absorption in the NIR region, also called “NIR window” or “transparent region” (between 700 and 1100 nm) often are preferable, because the radiation of longer wavelength can penetrate human tissues without causing any damage to the organism [ 3 , 4 ]. Interestingly, gold nanorods (GNR) can be synthesized in a manner that permits adjusting their SPR to the required biological NIR window [ 3 , 4 , 6 ]. A classic example of a material used in this context is polyethylene glycol (PEG), which increases the stability of the nanostructures in several media [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Encapsulation of Gold Nanostructures and Oil-in-Water Nanocarriers in Microgels with Biomedical Potential

et al. 2018

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Here we report the incorporation of gold nanostructures (nanospheres or nanorods, functionalized with carboxylate-end PEG) and curcumin oil-in-water (O/W) nanoemulsions (CurNem) into alginate microgels using the dripping technique. While gold nanostructures are promising nanomaterials for photothermal therapy applications, CurNem possess important pharmacological activities as reported here. In this sense, we evaluated the effect of CurNem on cell viability of both cancerous and non-cancerous cell lines (AGS and HEK293T, respectively), demonstrating preferential toxicity in cancer cells and safety for the non-cancerous cells. After incorporating gold nanostructures and CurNem together into the microgels, microstructures with diameters of 220 and 540 µm were obtained. When stimulating microgels with a laser, the plasmon effect promoted a significant rise in the temperature of the medium; the temperature increase was higher for those containing gold nanorods (11–12 °C) than nanospheres (1–2 °C). Interestingly, the incorporation of both nanosystems in the microgels maintains the photothermal properties of the gold nanostructures unmodified and retains with high efficiency the curcumin nanocarriers. We conclude that these results will be of interest to design hydrogel formulations with therapeutic applications.

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“…19 A powerful approach to drug delivery is based on the use of gold nanoparticles (AuNPs). [20][21][22][23] AuNPs can be conjugated to peptides, nucleic acids, and a wide range of small molecules; they provide a high surface-to-volume ratio, thereby maximizing the payload/carrier ratio and the coupling to other loading systems and making it possible to adjust the charge and hydrophobicity of the complex to maximize transfection efficiency while minimizing toxicity. 24,25 Several studies have demonstrated the biomedical potential of AuNPs.…”

Section: Introductionmentioning

confidence: 99%

Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia

Vio¹,

Riveros²,

Tapia-Bustos³

et al. 2018

IJN

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BackgroundPerinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated with systemic and neurological diseases. Despite the important role of poly (ADP-ribose) polymerase 1 (PARP-1) in the regulation of gene expression and DNA repair, overactivation of PARP-1 in asphyxia-exposed animals worsens the ATP-dependent energetic crisis. Inhibition of PARP-1 offers a therapeutic strategy for diminishing the effects of perinatal asphyxia.MethodsWe designed a nanosystem that incorporates a specific siRNA for PARP-1 knockdown. The siRNA was complexed with gold nanorods (AuNR) conjugated to the peptide CLPFFD for brain targeting.ResultsThe siRNA was efficiently delivered into PC12 cells, resulting in gene silencing. The complex was administered intraperitoneally in vivo to asphyxia-exposed rat pups, and the ability of the AuNR-CLPFFD/siRNA complex to reach the brain was demonstrated.ConclusionThe combination of a nanosystem for delivery and a specific siRNA for gene silencing resulted in effective inhibition of PARP-1 in vivo.

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Improving Gold Nanorod Delivery to the Central Nervous System By Conjugation to the Shuttle Angiopep-2

Abstract: This study provides evidence that Angiopep-2 improves the delivery of GNRs to the brain parenchyma. This property is highly relevant for future applications of GNRs as platforms for photothermal and theranostic purposes.

Cited by 42 publications

References 47 publications

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors

Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors

Encapsulation of Gold Nanostructures and Oil-in-Water Nanocarriers in Microgels with Biomedical Potential

Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia

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